Markers

This is the list of all markers present in GitHub Release.

Mutations on HA’s proteins are reported with H5 numbering. Mutations on NA’s protein are reported with N1 numbering.

Marker Effect Subtypes Literature
M1:N30D Increased virulence in mice H5N1 1, 2 1. Suttie A. et al., 2019
2. Fan S. et al., 2009
M1:T215A Increased virulence in mice H5N1 1, 2 1. Suttie A. et al., 2019
2. Fan S. et al., 2009
M1:I43M Increased virulence in chickens H5N1 1, 2 1. Nao N. et al., 2015
2. Suttie A. et al., 2019
M1:I43M Increased virulence in ducks H5N1 1, 2 1. Nao N. et al., 2015
2. Suttie A. et al., 2019
M1:I43M Increased virulence in mice H5N1 1, 2 1. Nao N. et al., 2015
2. Suttie A. et al., 2019
M2:L26F Increased resistance to amantadine H5N1 1, 2, 3, 4 1. Suttie A. et al., 2019
2. Abed Y. et al., 2005
3. Lan Y. et al., 2010
4. Bean W. et al., 1989
M2:L26F Increased resistance to rimantadine H5N1 1, 2, 3, 4 1. Suttie A. et al., 2019
2. Abed Y. et al., 2005
3. Lan Y. et al., 2010
4. Bean W. et al., 1989
M2:I27A Increased resistance to amantadine H5N1 1, 2, 3, 4, 5, 6
H5N2 1, 2, 3, 4, 5, 6		 1. Ilyushina N. et al., 2005
2. Suttie A. et al., 2019
3. Lan Y. et al., 2010
4. Bean W. et al., 1989
5. Abed Y. et al., 2005
6. Cheung C. et al., 2006
M2:I27A Increased resistance to rimantadine H5N1 1, 2, 3, 4, 5, 6
H5N2 1, 2, 3, 4, 5, 6		 1. Ilyushina N. et al., 2005
2. Suttie A. et al., 2019
3. Lan Y. et al., 2010
4. Bean W. et al., 1989
5. Abed Y. et al., 2005
6. Cheung C. et al., 2006
M2:I27T Increased resistance to amantadine H5N1 1, 2, 3, 4, 5, 6
H5N2 1, 2, 3, 4, 5, 6		 1. Ilyushina N. et al., 2005
2. Suttie A. et al., 2019
3. Lan Y. et al., 2010
4. Bean W. et al., 1989
5. Abed Y. et al., 2005
6. Cheung C. et al., 2006
M2:I27T Increased resistance to rimantadine H5N1 1, 2, 3, 4, 5, 6
H5N2 1, 2, 3, 4, 5, 6		 1. Ilyushina N. et al., 2005
2. Suttie A. et al., 2019
3. Lan Y. et al., 2010
4. Bean W. et al., 1989
5. Abed Y. et al., 2005
6. Cheung C. et al., 2006
M2:I27S Increased resistance to amantadine H5N1 1, 2, 3, 4, 5, 6
H5N2 1, 2, 3, 4, 5, 6		 1. Ilyushina N. et al., 2005
2. Suttie A. et al., 2019
3. Lan Y. et al., 2010
4. Bean W. et al., 1989
5. Abed Y. et al., 2005
6. Cheung C. et al., 2006
M2:I27S Increased resistance to rimantadine H5N1 1, 2, 3, 4, 5, 6
H5N2 1, 2, 3, 4, 5, 6		 1. Ilyushina N. et al., 2005
2. Suttie A. et al., 2019
3. Lan Y. et al., 2010
4. Bean W. et al., 1989
5. Abed Y. et al., 2005
6. Cheung C. et al., 2006
M2:A30V Increased resistance to amantadine H5N1 1, 2, 3, 4
H5N2 1, 2, 3, 4
H7N2 1, 2, 3, 4		 1. Cheung C. et al., 2006
2. Suttie A. et al., 2019
3. Ilyushina N. et al., 2005
4. Bean W. et al., 1989
M2:A30V Increased resistance to rimantadine H5N1 1, 2, 3, 4
H5N2 1, 2, 3, 4
H7N2 1, 2, 3, 4		 1. Cheung C. et al., 2006
2. Suttie A. et al., 2019
3. Ilyushina N. et al., 2005
4. Bean W. et al., 1989
M2:A30T Increased resistance to amantadine H5N1 1, 2, 3, 4
H5N2 1, 2, 3, 4
H7N2 1, 2, 3, 4		 1. Cheung C. et al., 2006
2. Suttie A. et al., 2019
3. Ilyushina N. et al., 2005
4. Bean W. et al., 1989
M2:A30T Increased resistance to rimantadine H5N1 1, 2, 3, 4
H5N2 1, 2, 3, 4
H7N2 1, 2, 3, 4		 1. Cheung C. et al., 2006
2. Suttie A. et al., 2019
3. Ilyushina N. et al., 2005
4. Bean W. et al., 1989
M2:A30S Increased resistance to amantadine H5N1 1, 2, 3, 4
H5N2 1, 2, 3, 4
H7N2 1, 2, 3, 4		 1. Cheung C. et al., 2006
2. Suttie A. et al., 2019
3. Ilyushina N. et al., 2005
4. Bean W. et al., 1989
M2:A30S Increased resistance to rimantadine H5N1 1, 2, 3, 4
H5N2 1, 2, 3, 4
H7N2 1, 2, 3, 4		 1. Cheung C. et al., 2006
2. Suttie A. et al., 2019
3. Ilyushina N. et al., 2005
4. Bean W. et al., 1989
M2:S31N Increased resistance to amantadine H5N1 1, 2, 3, 4, 5, 6, 7, 8
H5N2 1, 2, 3, 4, 5, 6, 7, 8
H9N2 1, 2, 3, 4, 5, 6, 7, 8		 1. Ilyushina N. et al., 2005
2. Puthavathana P. et al., 2005
3. Suttie A. et al., 2019
4. He G. et al., 2008
5. Lan Y. et al., 2010
6. Bean W. et al., 1989
7. Cheung C. et al., 2006
8. Buranathai C. et al., 2007
M2:S31N Increased resistance to rimantadine H5N1 1, 2, 3, 4, 5, 6, 7, 8
H5N2 1, 2, 3, 4, 5, 6, 7, 8
H9N2 1, 2, 3, 4, 5, 6, 7, 8		 1. Ilyushina N. et al., 2005
2. Puthavathana P. et al., 2005
3. Suttie A. et al., 2019
4. He G. et al., 2008
5. Lan Y. et al., 2010
6. Bean W. et al., 1989
7. Cheung C. et al., 2006
8. Buranathai C. et al., 2007
M2:S31G Increased resistance to amantadine H5N1 1, 2, 3, 4, 5, 6, 7, 8
H5N2 1, 2, 3, 4, 5, 6, 7, 8
H9N2 1, 2, 3, 4, 5, 6, 7, 8		 1. Ilyushina N. et al., 2005
2. Puthavathana P. et al., 2005
3. Suttie A. et al., 2019
4. He G. et al., 2008
5. Lan Y. et al., 2010
6. Bean W. et al., 1989
7. Cheung C. et al., 2006
8. Buranathai C. et al., 2007
M2:S31G Increased resistance to rimantadine H5N1 1, 2, 3, 4, 5, 6, 7, 8
H5N2 1, 2, 3, 4, 5, 6, 7, 8
H9N2 1, 2, 3, 4, 5, 6, 7, 8		 1. Ilyushina N. et al., 2005
2. Puthavathana P. et al., 2005
3. Suttie A. et al., 2019
4. He G. et al., 2008
5. Lan Y. et al., 2010
6. Bean W. et al., 1989
7. Cheung C. et al., 2006
8. Buranathai C. et al., 2007
M2:G34E Increased resistance to amantadine H5N1 1, 2 1. Suttie A. et al., 2019
2. Abed Y. et al., 2005
M2:G34E Increased resistance to rimantadine H5N1 1, 2 1. Suttie A. et al., 2019
2. Abed Y. et al., 2005
NS-1:P42S Decreased antiviral response in mice H5N1 1, 2 1. Jiao P. et al., 2008
2. Suttie A. et al., 2019
NS-1:P42S Increased virulence in mice H5N1 1, 2 1. Jiao P. et al., 2008
2. Suttie A. et al., 2019
NS-1:D74N Enhanced pathogenicity in mice H7N1 backbone with H5N1 NS 1, 2 1. Kanrai P. et al., 2016
2. Suttie A. et al., 2019
NS-1:D74N Enhanced replication in mammalian cells H7N1 backbone with H5N1 NS 1, 2 1. Kanrai P. et al., 2016
2. Suttie A. et al., 2019
NS-1:Y84F Decreased replication in mammalian cells H1N1 backbone with H5N1 NS 1, 2 1. Suttie A. et al., 2019
2. Wang B. et al., 2017
NS-1:Y84F Enhanced interferon response H1N1 backbone with H5N1 NS 1, 2 1. Suttie A. et al., 2019
2. Wang B. et al., 2017
NS-1:D92E Increased virulence in mice H1N1 backbone with H5N1 NS 2, 3, 4
H1N1 backbone with H5N1 HA, NA and NS 1, 3		 1. Long J. et al., 2008
2. Lipatov A. et al., 2005
3. Suttie A. et al., 2019
4. Seo S. et al., 2002
NS-1:D92E Increased virulence in swine H1N1 backbone with H5N1 NS 1, 2, 3 1. Lipatov A. et al., 2005
2. Suttie A. et al., 2019
3. Seo S. et al., 2002
NS-1:D92E Increased virulence in chickens H1N1 backbone with H5N1 HA, NA and NS 1, 2 1. Long J. et al., 2008
2. Suttie A. et al., 2019
NS-1:I106M Increased viral replication in mammalian cells H1N1 with all internal genes from H7N9 1, 2 1. Suttie A. et al., 2019
2. Ayllon J. et al., 2014
NS-1:I106M Increased virulence in mice H1N1 with all internal genes from H7N9 1, 2 1. Suttie A. et al., 2019
2. Ayllon J. et al., 2014
NS-1:C138F Decreased interferon response H5N1 1, 2 1. Suttie A. et al., 2019
2. Li J. et al., 2018
NS-1:C138F Increased viral replication in mammalian cells H5N1 1, 2 1. Suttie A. et al., 2019
2. Li J. et al., 2018
NS-1:V149A Decreased interferon response in chickens H5N1 1, 2 1. Li Z. et al., 2006
2. Suttie A. et al., 2019
NS-1:V149A Increased virulence in chickens H5N1 1, 2 1. Li Z. et al., 2006
2. Suttie A. et al., 2019
NS-1:L103F, NS-1:I106M Increased virulence in mice H5N1 1, 2, 3 1. Suttie A. et al., 2019
2. Spesock A. et al., 2011
3. Kuo R. et al., 2009
NS-1:N205S, NS-2:T48A Decreased antiviral response in ferrets H5N1 1, 2 1. Suttie A. et al., 2019
2. Imai H. et al., 2010
NS-1:G210R, NS-2:M51I Decreased antiviral response in ferrets H5N1 1, 2 1. Suttie A. et al., 2019
2. Imai H. et al., 2010
NS-1:D74N, NS-1:P3S, NS-1:R41K Enhanced pathogenicity in mice H7N1 backbone with H5N1 NS 1, 2 1. Kanrai P. et al., 2016
2. Suttie A. et al., 2019
NS-1:D74N, NS-1:P3S, NS-1:R41K Enhanced replication in mammalian cells H7N1 backbone with H5N1 NS 1, 2 1. Kanrai P. et al., 2016
2. Suttie A. et al., 2019
NS-1:R38A, NS-1:K41A Decreased replication in avian cells H7N1 1, 2 1. Trapp S. et al., 2018
2. Suttie A. et al., 2019
NS-1:R38A, NS-1:K41A Decreased replication in mammalian cells H7N1 1, 2 1. Trapp S. et al., 2018
2. Suttie A. et al., 2019
NS-1:C138F, NS-1:K55E, NS-1:K66E Decreased interferon response H5N1 1, 2 1. Suttie A. et al., 2019
2. Li J. et al., 2018
NS-1:C138F, NS-1:K55E, NS-1:K66E Enhanced replication in mammalian cells H5N1 1, 2 1. Suttie A. et al., 2019
2. Li J. et al., 2018
NS-2:M16I Increased polymerase activity in mammalian cells H5N1 1, 2 1. Reuther P. et al., 2014
2. Suttie A. et al., 2019
NS-2:M16I, NS-2:Y41C, NS-2:E75G Increased polymerase activity in mammalian cells H5N1 1, 2 1. Reuther P. et al., 2014
2. Suttie A. et al., 2019
NP:I41V Increased polymerase activity in mammalian cells H7N9 1, 2 1. Suttie A. et al., 2019
2. Zhu W. et al., 2015
NP:K91R Decreased polymerase activity in mammalian cells H5N1 1, 2 1. Suttie A. et al., 2019
2. Chen L. et al., 2017
NP:M105V Increased virulence in chickens H5N1 1, 2, 3 1. Tada T. et al., 2011
2. Suttie A. et al., 2019
3. Tada T. et al., 2011b
NP:I109T Increased polymerase activity in chickens (but not ducks) H5N1 1, 2, 3 1. Tada T. et al., 2011
2. Suttie A. et al., 2019
3. Tada T. et al., 2011b
NP:I109T Increased replication in chickens (but not ducks) H5N1 1, 2, 3 1. Tada T. et al., 2011
2. Suttie A. et al., 2019
3. Tada T. et al., 2011b
NP:I109T Increased virulence in chickens H5N1 1, 2, 3 1. Tada T. et al., 2011
2. Suttie A. et al., 2019
3. Tada T. et al., 2011b
NP:A184K Enhanced interferon response H5N1 1, 2 1. Suttie A. et al., 2019
2. Wasilenko J. et al., 2009
NP:A184K Increased replication in avian cells H5N1 1, 2 1. Suttie A. et al., 2019
2. Wasilenko J. et al., 2009
NP:A184K Increased virulence in chickens H5N1 1, 2 1. Suttie A. et al., 2019
2. Wasilenko J. et al., 2009
NP:K198R Decreased polymerase activity in mammalian cells H5N1 1, 2 1. Suttie A. et al., 2019
2. Chen L. et al., 2017
NP:E210D Increased polymerase activity in mammalian cells H7N9 1, 2 1. Suttie A. et al., 2019
2. Zhu W. et al., 2015
NP:K227R Increased polymerase activity in mammalian cells H5N1 1, 2 1. Suttie A. et al., 2019
2. Chen L. et al., 2017
NP:K229R Increased polymerase activity in mammalian cells H5N1 1, 2 1. Suttie A. et al., 2019
2. Chen L. et al., 2017
NP:N319K Increased polymerase activity in mammalian cells H7N7 1, 2, 3 1. Gabriel G. et al., 2008
2. Gabriel G. et al., 2005
3. Suttie A. et al., 2019
NP:N319K Increased replication in mammalian cells H7N7 1, 2, 3 1. Gabriel G. et al., 2008
2. Gabriel G. et al., 2005
3. Suttie A. et al., 2019
NP:E434K Increased polymerase activity in mammalian cells H9N2 1, 2 1. Suttie A. et al., 2019
2. Sang X. et al., 2015b
NP:K470R Increased polymerase activity in mammalian cells H5N1 1, 2 1. Suttie A. et al., 2019
2. Chen L. et al., 2017
NP:K470R Increased replication in mammalian cells H5N1 1, 2 1. Suttie A. et al., 2019
2. Chen L. et al., 2017
NP:K470R Increased virulence in mice H5N1 1, 2 1. Suttie A. et al., 2019
2. Chen L. et al., 2017
NP:Q357L, PB2:E627K Increased virulence in mice H5N1 1, 2 1. Suttie A. et al., 2019
2. Kim J. et al., 2010
PB2:D9N Increased virulence in mice H5N1 1, 2, 3 1. Suttie A. et al., 2019
2. Graef K. et al., 2010
3. Kim J. et al., 2010
PB2:V25A Increased virulence in mice H5N1 backbone with H1N1 NS 1, 2 1. Suttie A. et al., 2019
2. Zhao D. et al., 2015
PB2:I63T Decreased pathogenicity in mice H5N1 1, 2 1. Li J. et al., 2011
2. Suttie A. et al., 2019
PB2:E158G Increased polymerase activity in avian cells H5N1 1 1. Cauldwell A. et al., 2013
PB2:E158G Increased polymerase activity in mammalian cells H5N1 1
H5N2 2, 3
H5N9 2, 3		 1. Cauldwell A. et al., 2013
2. Zhou B. et al., 2011
3. Suttie A. et al., 2019
PB2:E158G Increased virulence in mice H5N2 1, 2
H5N9 1, 2		 1. Zhou B. et al., 2011
2. Suttie A. et al., 2019
PB2:E158K Increased polymerase activity in mammalian cells H4N6 1, 2 1. Suttie A. et al., 2019
2. Xu G. et al., 2020
PB2:E158K Increased replication in mammalian cells H4N6 1, 2 1. Suttie A. et al., 2019
2. Xu G. et al., 2020
PB2:E158K Increased virulence in mice H4N6 1, 2 1. Suttie A. et al., 2019
2. Xu G. et al., 2020
PB2:E192K Increased polymerase activity in avian cells H5N1 1, 2 1. Taft A. et al., 2015
2. Suttie A. et al., 2019
PB2:E192K Increased polymerase activity in mammalian cells H5N1 1, 2 1. Taft A. et al., 2015
2. Suttie A. et al., 2019
PB2:E192K Increased virulence in mice H5N1 1, 2 1. Taft A. et al., 2015
2. Suttie A. et al., 2019
PB2:A199S Increased virulence in mice H5N1 1, 2 1. Suttie A. et al., 2019
2. Kim J. et al., 2010
PB2:D253N Increased polymerase activity in mammalian cells H9N2 1, 2 1. Zhang J. et al., 2018
2. Suttie A. et al., 2019
PB2:D256G Increased polymerase activity in mammalian cells H5N1 backbone with pH1N1 PB2 1, 2 1. Manzoor R. et al., 2009
2. Suttie A. et al., 2019
PB2:T271A Increased polymerase activity in avian cells H3N2 (avian) 1, 2, 3, 4
H5N1 1, 2, 3, 4, 5
H7N9 1, 2, 3, 4		 1. Mok C. et al., 2014
2. Suttie A. et al., 2019
3. Foeglein Á. et al., 2011
4. Bussey K. et al., 2010
5. Peacock T. et al., 2023
PB2:T271A Increased polymerase activity in mammalian cells H1N1 4
H3N2 (avian) 1, 2, 3, 4
H5N1 1, 2, 3, 4, 5, 6
H7N9 1, 2, 3, 4		 1. Mok C. et al., 2014
2. Suttie A. et al., 2019
3. Foeglein Á. et al., 2011
4. Bussey K. et al., 2010
5. Cauldwell A. et al., 2013
6. Peacock T. et al., 2023
PB2:T271A Enhanced contact transmission in ferrets H5N1 1 1. Restori K. et al., 2024
PB2:T271A Enhanced replication in ferrets H5N1 1 1. Restori K. et al., 2024
PB2:T271A Transmitted via aerosol among ferrets H5N1 1 1. Restori K. et al., 2024
PB2:I292V Increased polymerase activity in mammalian cells H9N2 1, 2
H10N8 1, 3		 1. Suttie A. et al., 2019
2. Gao W. et al., 2019
3. Xiao C. et al., 2016
PB2:I292V Increased virulence in mice H9N2 1, 2 1. Suttie A. et al., 2019
2. Gao W. et al., 2019
PB2:E358V Decreased virulence in mice H7N3 1, 2 1. Suttie A. et al., 2019
2. DesRochers B. et al., 2016
PB2:K389R Increased polymerase activity in mammalian cells H7N9 1, 2 1. Suttie A. et al., 2019
2. Hu M. et al., 2017b
PB2:K389R Increased replication in mammalian cells H7N9 1, 2 1. Suttie A. et al., 2019
2. Hu M. et al., 2017b
PB2:L339T Decreased polymerase activity in mice H5N1 1, 2 1. Suttie A. et al., 2019
2. Liu Y. et al., 2013
PB2:L339T Decreased virulence in mice H5N1 1, 2 1. Suttie A. et al., 2019
2. Liu Y. et al., 2013
PB2:K482R Increased polymerase activity in mammalian cells H7N9 1, 2, 3 1. Yamayoshi S. et al., 2018
2. Yamayoshi S. et al., 2014
3. Suttie A. et al., 2019
PB2:K526R Increased polymerase activity in mammalian cells H5N1 1, 2
H7N9 1, 2		 1. Song W. et al., 2014
2. Suttie A. et al., 2019
PB2:M535L Increased polymerase activity in mammalian cells H7N9 1, 2 1. Chen G. et al., 2016
2. Suttie A. et al., 2019
PB2:A588V Increased polymerase activity in avian cells H10N8 1, 2
H7N9 1, 2
H9N2 1, 2		 1. Suttie A. et al., 2019
2. Xiao C. et al., 2016
PB2:A588V Increased polymerase activity in mammalian cells H10N8 1, 2
H7N9 1, 2
H9N2 1, 2		 1. Suttie A. et al., 2019
2. Xiao C. et al., 2016
PB2:A588V Increased replication in avian cells H10N8 1, 2
H7N9 1, 2
H9N2 1, 2		 1. Suttie A. et al., 2019
2. Xiao C. et al., 2016
PB2:A588V Increased replication in mammalian cells H10N8 1, 2
H7N9 1, 2
H9N2 1, 2		 1. Suttie A. et al., 2019
2. Xiao C. et al., 2016
PB2:A588V Increased virulence in mice H10N8 1, 2
H7N9 1, 2
H9N2 1, 2		 1. Suttie A. et al., 2019
2. Xiao C. et al., 2016
PB2:Q591K Increased polymerase activity in avian cells H7N9 1, 2, 5
H5N1 2, 3, 4		 1. Mok C. et al., 2014
2. Suttie A. et al., 2019
3. Shinya Y. et al., 2010
4. Taft A. et al., 2015
5. Chen G. et al., 2016
PB2:Q591K Increased polymerase activity in mammalian cells H7N9 1, 2, 6
H5N1 2, 3, 5
H9N2 2, 4		 1. Mok C. et al., 2014
2. Suttie A. et al., 2019
3. Shinya Y. et al., 2010
4. Wang C. et al., 2016
5. Taft A. et al., 2015
6. Chen G. et al., 2016
PB2:Q591K Increased replication in mammalian cells H5N1 1, 2, 4
H9N2 2, 3		 1. Taft A. et al., 2015
2. Suttie A. et al., 2019
3. Wang C. et al., 2016
4. Shinya Y. et al., 2010
PB2:Q591K Increased virulence in mice H5N1 1, 2, 4
H9N2 2, 3		 1. Taft A. et al., 2015
2. Suttie A. et al., 2019
3. Wang C. et al., 2016
4. Shinya Y. et al., 2010
PB2:V598T Increased polymerase activity in mammalian cells H7N9 1, 2 1. Suttie A. et al., 2019
2. Hu M. et al., 2017b
PB2:V598T Increased replication in mammalian cells H7N9 1, 2 1. Suttie A. et al., 2019
2. Hu M. et al., 2017b
PB2:V598T Increased virulence in mice H7N9 1, 2 1. Suttie A. et al., 2019
2. Hu M. et al., 2017b
PB2:V598I Increased polymerase activity in mammalian cells H7N9 1, 2 1. Suttie A. et al., 2019
2. Hu M. et al., 2017b
PB2:V598I Increased replication in mammalian cells H7N9 1, 2 1. Suttie A. et al., 2019
2. Hu M. et al., 2017b
PB2:V598I Increased virulence in mice H7N9 1, 2 1. Suttie A. et al., 2019
2. Hu M. et al., 2017b
PB2:E627K Contributes to airborne pathogenicity in ferrets H5N1 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15 1. Manzoor R. et al., 2009
2. Long J. et al., 2013
3. Chen H. et al., 2007
4. Hatta M. et al., 2007
5. Herfst S. et al., 2012
6. Shinya K. et al., 2004
7. Suttie A. et al., 2019
8. Richard M. et al., 2017
9. Mase M. et al., 2006
10. Le Q. et al., 2005
11. Hatta H. et al., 2001
12. Fornek J. et al., 2009
13. Kim J. et al., 2010
14. Bogs J. et al., 2011
15. Bortz E. et al., 2011
PB2:E627K Contributes to contact transmission in guinea pigs H5N1 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15 1. Manzoor R. et al., 2009
2. Long J. et al., 2013
3. Chen H. et al., 2007
4. Hatta M. et al., 2007
5. Herfst S. et al., 2012
6. Shinya K. et al., 2004
7. Suttie A. et al., 2019
8. Richard M. et al., 2017
9. Mase M. et al., 2006
10. Le Q. et al., 2005
11. Hatta H. et al., 2001
12. Fornek J. et al., 2009
13. Kim J. et al., 2010
14. Bogs J. et al., 2011
15. Bortz E. et al., 2011
PB2:E627K Decreased polymerase activity in avian cells H5N1 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15 1. Manzoor R. et al., 2009
2. Long J. et al., 2013
3. Chen H. et al., 2007
4. Hatta M. et al., 2007
5. Herfst S. et al., 2012
6. Shinya K. et al., 2004
7. Suttie A. et al., 2019
8. Richard M. et al., 2017
9. Mase M. et al., 2006
10. Le Q. et al., 2005
11. Hatta H. et al., 2001
12. Fornek J. et al., 2009
13. Kim J. et al., 2010
14. Bogs J. et al., 2011
15. Bortz E. et al., 2011
PB2:E627K Decreased replication in avian cells H5N1 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15 1. Manzoor R. et al., 2009
2. Long J. et al., 2013
3. Chen H. et al., 2007
4. Hatta M. et al., 2007
5. Herfst S. et al., 2012
6. Shinya K. et al., 2004
7. Suttie A. et al., 2019
8. Richard M. et al., 2017
9. Mase M. et al., 2006
10. Le Q. et al., 2005
11. Hatta H. et al., 2001
12. Fornek J. et al., 2009
13. Kim J. et al., 2010
14. Bogs J. et al., 2011
15. Bortz E. et al., 2011
PB2:E627K Decreases virulence in chickens H5N1 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15 1. Manzoor R. et al., 2009
2. Long J. et al., 2013
3. Chen H. et al., 2007
4. Hatta M. et al., 2007
5. Herfst S. et al., 2012
6. Shinya K. et al., 2004
7. Suttie A. et al., 2019
8. Richard M. et al., 2017
9. Mase M. et al., 2006
10. Le Q. et al., 2005
11. Hatta H. et al., 2001
12. Fornek J. et al., 2009
13. Kim J. et al., 2010
14. Bogs J. et al., 2011
15. Bortz E. et al., 2011
PB2:E627K Enhanced polymerase activity H5N1 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15 1. Manzoor R. et al., 2009
2. Long J. et al., 2013
3. Chen H. et al., 2007
4. Hatta M. et al., 2007
5. Herfst S. et al., 2012
6. Shinya K. et al., 2004
7. Suttie A. et al., 2019
8. Richard M. et al., 2017
9. Mase M. et al., 2006
10. Le Q. et al., 2005
11. Hatta H. et al., 2001
12. Fornek J. et al., 2009
13. Kim J. et al., 2010
14. Bogs J. et al., 2011
15. Bortz E. et al., 2011
PB2:E627K Increased virulence in mice H5N1 1, 3, 5, 6, 7, 8, 9, 10, 11, 13, 15, 16, 18, 20, 22
H6N1 4, 20
H7N7 12, 20, 21
H9N2 12, 17, 20
H7N9 2, 12, 20
H4N6 14, 20
H6N6 19		 1. Hatta M. et al., 2007
2. Zhang H. et al., 2014
3. Hatta H. et al., 2001
4. Cheng K. et al., 2014
5. Herfst S. et al., 2012
6. Manzoor R. et al., 2009
7. Long J. et al., 2013
8. Chen H. et al., 2007
9. Shinya K. et al., 2004
10. Mase M. et al., 2006
11. Kim J. et al., 2010
12. Sediri H. et al., 2016
13. Richard M. et al., 2017
14. Xu G. et al., 2020
15. Le Q. et al., 2005
16. Fornek J. et al., 2009
17. Sang X. et al., 2015
18. Bortz E. et al., 2011
19. Tan L. et al., 2014
20. Suttie A. et al., 2019
21. De Jong R. et al., 2013
22. Bogs J. et al., 2011
PB2:E627K Increased polymerase activity in mammalian cells H5N1 5, 6
H6N1 1, 8
H9N2 1, 2, 7
H7N9 1, 2, 3
H4N6 1, 4		 1. Suttie A. et al., 2019
2. Sediri H. et al., 2016
3. Zhang H. et al., 2014
4. Xu G. et al., 2020
5. Cauldwell A. et al., 2013
6. Peacock T. et al., 2023
7. Sang X. et al., 2015
8. Cheng K. et al., 2014
PB2:E627K Increased polymerase activity in avian cells H7N7 1, 2, 3 1. De Jong R. et al., 2013
2. Sediri H. et al., 2016
3. Suttie A. et al., 2019
PB2:E627K Increased virulence in ferrets H7N7 1, 2, 3 1. De Jong R. et al., 2013
2. Sediri H. et al., 2016
3. Suttie A. et al., 2019
PB2:E627K Increased replication in mammalian cells H7N9 1, 2, 3
H4N6 1, 4		 1. Suttie A. et al., 2019
2. Sediri H. et al., 2016
3. Zhang H. et al., 2014
4. Xu G. et al., 2020
PB2:E627V Increased polymerase activity in mammalian cells H5N1 1, 2 1. Taft A. et al., 2015
2. Suttie A. et al., 2019
PB2:E627V Increased replication in mammalian cells H5N1 1, 2 1. Taft A. et al., 2015
2. Suttie A. et al., 2019
PB2:E627V Increased virulence in mice H5N1 1, 2 1. Taft A. et al., 2015
2. Suttie A. et al., 2019
PB2:D701N Increased polymerase activity in mammalian cells H5N1 4, 5
H7N9 1, 2, 6
H9N2 2, 3		 1. Mok C. et al., 2014
2. Suttie A. et al., 2019
3. Sediri H. et al., 2016
4. Cauldwell A. et al., 2013
5. Peacock T. et al., 2023
6. Chen G. et al., 2016
PB2:D701N Enhanced replication in mice H7N9 1, 2, 3 1. Chen G. et al., 2016
2. Mok C. et al., 2014
3. Suttie A. et al., 2019
PB2:D701N Contact transmission in guinea pigs H5N1 1, 2, 3, 4, 5, 6 1. Gao Y. et al., 2009
2. Li Z. et al., 2005
3. Le Q. et al., 2009
4. Suttie A. et al., 2019
5. Taft A. et al., 2015
6. Steel J. et al., 2009
PB2:D701N Enhanced replication in guinea pigs H5N1 1, 2, 3, 4, 5, 6 1. Gao Y. et al., 2009
2. Li Z. et al., 2005
3. Le Q. et al., 2009
4. Suttie A. et al., 2019
5. Taft A. et al., 2015
6. Steel J. et al., 2009
PB2:D701N Increased polymerase activity in guinea pigs H5N1 1, 2, 3, 4, 5, 6 1. Gao Y. et al., 2009
2. Li Z. et al., 2005
3. Le Q. et al., 2009
4. Suttie A. et al., 2019
5. Taft A. et al., 2015
6. Steel J. et al., 2009
PB2:D701N Increased virulence in guinea pigs H5N1 1, 2, 3, 4, 5, 6 1. Gao Y. et al., 2009
2. Li Z. et al., 2005
3. Le Q. et al., 2009
4. Suttie A. et al., 2019
5. Taft A. et al., 2015
6. Steel J. et al., 2009
PB2:D701N Increased virulence in mice H5N1 1, 2, 4, 5, 6, 7
H1N2 3, 5		 1. Gao Y. et al., 2009
2. Li Z. et al., 2005
3. Yu Z. et al., 2019
4. Le Q. et al., 2009
5. Suttie A. et al., 2019
6. Taft A. et al., 2015
7. Steel J. et al., 2009
PB2:D701N Increased viral replication in mammalian cells H1N2 1, 2 1. Suttie A. et al., 2019
2. Yu Z. et al., 2019
PB2:D701V Increased polymerase activity in mammalian cells H5N1 1, 2 1. Taft A. et al., 2015
2. Suttie A. et al., 2019
PB2:D701V Increased replication in mammalian cells H5N1 1, 2 1. Taft A. et al., 2015
2. Suttie A. et al., 2019
PB2:D701V Increased virulence in mice H5N1 1, 2 1. Taft A. et al., 2015
2. Suttie A. et al., 2019
PB2:S714R Increased polymerase activity in mammalian cells H7N7 1, 2, 3, 4
H9N2 2, 3		 1. Gabriel G. et al., 2005
2. Suttie A. et al., 2019
3. Sediri H. et al., 2016
4. Gabriel G. et al., 2007
PB2:S714R Increased replication in mammalian cells H7N7 1, 2, 3, 4 1. Gabriel G. et al., 2005
2. Suttie A. et al., 2019
3. Sediri H. et al., 2016
4. Gabriel G. et al., 2007
PB2:S715N Decreased virulence in mice H5N1 1, 2 1. Sun H. et al., 2015
2. Suttie A. et al., 2019
PB2:M28I, PB2:A274T, PB2:K526R, PB2:I553V, PB2:L607V Decreased polymerase activity in mammalian cells H5N1 1, 2 1. Leung B. et al., 2010
2. Suttie A. et al., 2019
PB2:L89V, PB2:G309D Increased polymerase activity in mammalian cells H5N1 1, 2 1. Li J. et al., 2009
2. Suttie A. et al., 2019
PB2:L89V, PB2:G309D Increased virulence in mice H5N1 1, 2 1. Li J. et al., 2009
2. Suttie A. et al., 2019
PB2:L89V, PB2:G309D, PB2:T339K, PB2:R477G, PB2:I495V, PB2:K627E, PB2:A676T Increased polymerase activity in mammalian cells H5N1 1, 2 1. Li J. et al., 2009
2. Suttie A. et al., 2019
PB2:L89V, PB2:G309D, PB2:T339K, PB2:R477G, PB2:I495V, PB2:K627E, PB2:A676T Increased virulence in mice H5N1 1, 2 1. Li J. et al., 2009
2. Suttie A. et al., 2019
PB2:M147L, PB2:E627K Increased polymerase activity in mammalian cells H9N2 1, 2 1. Wang J. et al., 2012
2. Suttie A. et al., 2019
PB2:M147L, PB2:E627K Increased virulence in mice H9N2 1, 2 1. Wang J. et al., 2012
2. Suttie A. et al., 2019
PB2:I147T, PB2:K339T, PB2:A588T Increased polymerase activity in mammalian cells H5N1 1, 2 1. Fan S. et al., 2014
2. Suttie A. et al., 2019
PB2:I147T, PB2:K339T, PB2:A588T Increased virulence in mice H5N1 1, 2 1. Fan S. et al., 2014
2. Suttie A. et al., 2019
PB2:K526R, PB2:E627K Increased polymerase activity in mammalian cells H5N1 1, 2
H7N9 1, 2		 1. Song W. et al., 2014
2. Suttie A. et al., 2019
PB2:K526R, PB2:E627K Increased replication in mammalian cells H5N1 1, 2
H7N9 1, 2		 1. Song W. et al., 2014
2. Suttie A. et al., 2019
PB2:K526R, PB2:E627K Increased virulence in mice H5N1 1, 2
H7N9 1, 2		 1. Song W. et al., 2014
2. Suttie A. et al., 2019
PB2:E627K, PB2:D701N Increased polymerase activity in mammalian cells H7N9 1, 2 1. Suttie A. et al., 2019
2. Zhu W. et al., 2015
PB2:E627K, PB2:S714R Increased polymerase activity in mammalian cells H7N7 1, 2
H7N9 1, 2
H9N2 1, 2		 1. Suttie A. et al., 2019
2. Sediri H. et al., 2016
PB2:E627K, PB2:D701N, PB2:S714R Increased polymerase activity in mammalian cells H9N2 1, 2 1. Suttie A. et al., 2019
2. Sediri H. et al., 2016
PB2:E627K, PB2:D701N, PB2:S714R Increased virulence in mice H9N2 1, 2 1. Suttie A. et al., 2019
2. Sediri H. et al., 2016
PB2:D701N, PB2:S714R Increased replication in mammalian cells H5N1 1, 2 1. Suttie A. et al., 2019
2. Czudai-Matwich V. et al., 2014
PB2:D701N, PB2:S714R Increased virulence in mice H5N1 1, 2 1. Suttie A. et al., 2019
2. Czudai-Matwich V. et al., 2014
PB2:D701N, PB2:S714R Increased polymerase activity in mammalian cells H7N7 1, 2
H7N9 1, 2
H9N2 1, 2		 1. Suttie A. et al., 2019
2. Sediri H. et al., 2016
PB1:D3V Increased polymerase activity in avian cells H5N1 1, 2 1. Elgendy E. et al., 2017
2. Suttie A. et al., 2019
PB1:D3V Increased polymerase activity in mammalian cells H5N1 1, 2 1. Elgendy E. et al., 2017
2. Suttie A. et al., 2019
PB1:D3V Increased replication in avian cells H5N1 1, 2 1. Elgendy E. et al., 2017
2. Suttie A. et al., 2019
PB1:D3V Increased replication in mammalian cells H5N1 1, 2 1. Elgendy E. et al., 2017
2. Suttie A. et al., 2019
PB1:N105S Increased polymerase activity in mammalian cells H5N1 1, 2 1. Taft A. et al., 2015
2. Suttie A. et al., 2019
PB1:N105S Increased replication in mammalian cells H5N1 1, 2 1. Taft A. et al., 2015
2. Suttie A. et al., 2019
PB1:N105S Increased virulence in mice H5N1 1, 2 1. Taft A. et al., 2015
2. Suttie A. et al., 2019
PB1:K207R Decreased polymerase activity in mammalian cells H5N1 1, 2 1. Suttie A. et al., 2019
2. Hulse-Post D. et al., 2007
PB1:Y436H Decreased polymerase activity in mammalian cells H5N1 1, 2 1. Suttie A. et al., 2019
2. Hulse-Post D. et al., 2007
PB1:Y436H Decreased virulence in ducks H5N1 1, 2 1. Suttie A. et al., 2019
2. Hulse-Post D. et al., 2007
PB1:Y436H Decreased virulence in ferrets H5N1 1, 2 1. Suttie A. et al., 2019
2. Hulse-Post D. et al., 2007
PB1:Y436H Decreased virulence in mice H5N1 1, 2 1. Suttie A. et al., 2019
2. Hulse-Post D. et al., 2007
PB1:V473L Decreased polymerase activity in mammalian cells H1N1 backbone with H5N1 PB2, PB1, PA and NP 1, 2 1. Suttie A. et al., 2019
2. Xu C. et al., 2012
PB1:V473L Decreased replication in mammalian cells H1N1 backbone with H5N1 PB2, PB1, PA and NP 1, 2 1. Suttie A. et al., 2019
2. Xu C. et al., 2012
PB1:K577E Increased polymerase activity in mammalian cells H9N2 1, 2 1. Kamiki H. et al., 2018
2. Suttie A. et al., 2019
PB1:K577E Increased polymerase activity in mice H9N2 1, 2 1. Kamiki H. et al., 2018
2. Suttie A. et al., 2019
PB1:K577E Increased virulence in mice H9N2 1, 2 1. Kamiki H. et al., 2018
2. Suttie A. et al., 2019
PB1:V598P Decreased polymerase activity in mammalian cells H1N1 backbone with H5N1 PB2, PB1, PA and NP 1, 2 1. Suttie A. et al., 2019
2. Xu C. et al., 2012
PB1:V598P Decreased replication in mammalian cells H1N1 backbone with H5N1 PB2, PB1, PA and NP 1, 2 1. Suttie A. et al., 2019
2. Xu C. et al., 2012
PB1:D622G Increased polymerase activity in mammalian cells H5N1 1, 2 1. Suttie A. et al., 2019
2. Feng X. et al., 2016
PB1:D622G Increased polymerase activity in mice H5N1 1, 2 1. Suttie A. et al., 2019
2. Feng X. et al., 2016
PB1:D622G Increased virulence in mice H5N1 1, 2 1. Suttie A. et al., 2019
2. Feng X. et al., 2016
PB1:T677M Decreased replication in mammalian cells H5N1 1, 2 1. Li J. et al., 2011b
2. Suttie A. et al., 2019
PB1:T677M Decreased virulence in mice H5N1 1, 2 1. Li J. et al., 2011b
2. Suttie A. et al., 2019
PB1:T677M Increased polymerase activity in mammalian cells H5N1 1, 2 1. Li J. et al., 2011b
2. Suttie A. et al., 2019
PB1:S678N Increased replication in avian cells H7N7 1, 2 1. Gabriel G. et al., 2007
2. Suttie A. et al., 2019
PB1:S678N Increased replication in mammalian cells H7N7 1, 2 1. Gabriel G. et al., 2007
2. Suttie A. et al., 2019
PB1:V3A, PB1:N328K, PB1:N375S Decreased replication in ferrets H5N1 1, 2 1. Salomon R. et al., 2006
2. Suttie A. et al., 2019
PB1:V3A, PB1:N328K, PB1:N375S Decreased virulence in ferrets H5N1 1, 2 1. Salomon R. et al., 2006
2. Suttie A. et al., 2019
PB1:V473L, PB1:P598L Decreased polymerase activity in mammalian cells H1N1 backbone with H5N1 PB2, PB1, PA and NP 1, 2 1. Suttie A. et al., 2019
2. Xu C. et al., 2012
PB1:V473L, PB1:P598L Decreased replication in mammalian cells H1N1 backbone with H5N1 PB2, PB1, PA and NP 1, 2 1. Suttie A. et al., 2019
2. Xu C. et al., 2012
PB1-F2:N66S Enhanced antiviral response in mice H5N1 1, 2, 3 1. Schmolke M. et al., 2011
2. Suttie A. et al., 2019
3. Conenello G. et al., 2007
PB1-F2:N66S Enhanced replication in mice H5N1 1, 2, 3 1. Schmolke M. et al., 2011
2. Suttie A. et al., 2019
3. Conenello G. et al., 2007
PB1-F2:N66S Enhanced virulence in mice H5N1 1, 2, 3 1. Schmolke M. et al., 2011
2. Suttie A. et al., 2019
3. Conenello G. et al., 2007
PB1-F2:T51M, PB1-F2:V56A, PB1-F2:E87G Decreased polymerase activity in ducks H5N1 1, 2 1. Marjuki H. et al., 2010
2. Suttie A. et al., 2019
PB1-F2:T51M, PB1-F2:V56A, PB1-F2:E87G Decreased replication in ducks H5N1 1, 2 1. Marjuki H. et al., 2010
2. Suttie A. et al., 2019
PB1-F2:T51M, PB1-F2:V56A, PB1-F2:E87G Decreased virulence in ducks H5N1 1, 2 1. Marjuki H. et al., 2010
2. Suttie A. et al., 2019
PA:S37A Increased polymerase activity in mammalian cells H7N9 1, 2 1. Yamayoshi S. et al., 2014
2. Suttie A. et al., 2019
PA:A37S Decreased polymerase activity in mammalian cells H7N7 1, 2 1. Suttie A. et al., 2019
2. Hu M. et al., 2017
PA:V63I Enhanced replication in mammalian cells H7N7 1, 2, 3 1. Suttie A. et al., 2019
2. Hu M. et al., 2017
3. Hu M. et al., 2016
PA:V63I Increased polymerase activity in mammalian cells H7N7 1, 2, 3 1. Suttie A. et al., 2019
2. Hu M. et al., 2017
3. Hu M. et al., 2016
PA:V63I Increased virulence in mice H7N7 1, 2, 3 1. Suttie A. et al., 2019
2. Hu M. et al., 2017
3. Hu M. et al., 2016
PA:T97I Increased polymerase activity in mammalian cells H6N1 2, 3
H5N2 1, 2
H5N1 2, 4		 1. Song M. et al., 2009
2. Suttie A. et al., 2019
3. Cheng K. et al., 2014
4. Taft A. et al., 2015
PA:T97I Increased virulence in mice H6N1 2, 3
H5N2 1, 2
H5N1 2, 4		 1. Song M. et al., 2009
2. Suttie A. et al., 2019
3. Cheng K. et al., 2014
4. Taft A. et al., 2015
PA:T97I Increased replication in mammalian cells H5N1 1, 2 1. Taft A. et al., 2015
2. Suttie A. et al., 2019
PA:K142N Increased virulence in mice H5N1 1, 2 1. Suttie A. et al., 2019
2. Kim J. et al., 2010
PA:K142E, PB2:E627K Increased virulence in mice H5N1 1, 2 1. Suttie A. et al., 2019
2. Kim J. et al., 2010
PA:K158R Increased polymerase activity in mammalian cells H5N1 1, 2 1. Elgendy E. et al., 2017
2. Suttie A. et al., 2019
PA:P190S Decreased virulence in mice H7N3 1, 2 1. Suttie A. et al., 2019
2. DesRochers B. et al., 2016
PA:K356R Enhanced replication in mammalian cells H9N2 1, 2 1. Xu G. et al., 2016
2. Suttie A. et al., 2019
PA:K356R Increased polymerase activity in mammalian cells H9N2 1, 2 1. Xu G. et al., 2016
2. Suttie A. et al., 2019
PA:K356R Increased virulence in mice H9N2 1, 2 1. Xu G. et al., 2016
2. Suttie A. et al., 2019
PA:N383D Increased polymerase activity in avian cells H5N1 1, 2, 3 1. Suttie A. et al., 2019
2. Song J. et al., 2015
3. Song J. et al., 2011
PA:N383D Increased polymerase activity in mammalian cells H5N1 1, 2, 3 1. Suttie A. et al., 2019
2. Song J. et al., 2015
3. Song J. et al., 2011
PA:Q400P Decreased virulence in mice H7N3 1, 2 1. Suttie A. et al., 2019
2. DesRochers B. et al., 2016
PA:N409S Increased polymerase activity in mammalian cells H7N9 1, 2 1. Yamayoshi S. et al., 2014
2. Suttie A. et al., 2019
PA:N409S Increased replication in mammalian cells H7N9 1, 2 1. Yamayoshi S. et al., 2014
2. Suttie A. et al., 2019
PA:S421I Increased virulence in mice H5N1 1, 2 1. Suttie A. et al., 2019
2. Kim J. et al., 2010
PA:R443K Increased virulence in mice H5N1 1, 2 1. Suttie A. et al., 2019
2. Zhao D. et al., 2015
PA:K497R Increased polymerase activity in mammalian cells H7N9 (human isolate) 1, 2 1. Yamayoshi S. et al., 2018
2. Suttie A. et al., 2019
PA:T515A Decreased polymerase activity in mammalian cells H5N1 1, 2 1. Suttie A. et al., 2019
2. Gao H. et al., 2015b
PA:T515A Decreased virulence in ducks H5N1 1, 2 1. Suttie A. et al., 2019
2. Gao H. et al., 2015b
PA:K615N Increased polymerase activity in mammalian cells H7N7 1, 2, 3 1. Gabriel G. et al., 2005
2. Suttie A. et al., 2019
3. Gabriel G. et al., 2007
PA:K615N Increased virulence in mice H7N7 1, 2, 3 1. Gabriel G. et al., 2005
2. Suttie A. et al., 2019
3. Gabriel G. et al., 2007
PA:A343S, PA:D347E Increased polymerase activity in mammalian cells H5N1 1, 2 1. Suttie A. et al., 2019
2. Zhong G. et al., 2018
PA:A343S, PA:D347E Increased virulence in mice H5N1 1, 2 1. Suttie A. et al., 2019
2. Zhong G. et al., 2018
PA:P103H, PA:S659L Decreased polymerase activity in mammalian cells H7N7 1, 2 1. Suttie A. et al., 2019
2. Gao P. et al., 2018
PA:P103H, PA:S659L Decreased virulence in mice H7N7 1, 2 1. Suttie A. et al., 2019
2. Gao P. et al., 2018
PA:S224P, PA:N383D Enhanced replication in duck cells H5N1 1, 2, 3 1. Leung B. et al., 2010
2. Suttie A. et al., 2019
3. Xiao C. et al., 2016
PA:S224P, PA:N383D Enhanced replication in mice cells H5N1 1, 2, 3 1. Leung B. et al., 2010
2. Suttie A. et al., 2019
3. Xiao C. et al., 2016
PA:S224P, PA:N383D Increased polymerase activity in duck cells H5N1 1, 2, 3 1. Leung B. et al., 2010
2. Suttie A. et al., 2019
3. Xiao C. et al., 2016
PA:S224P, PA:N383D Increased polymerase activity in mice cells H5N1 1, 2, 3 1. Leung B. et al., 2010
2. Suttie A. et al., 2019
3. Xiao C. et al., 2016
PA:S224P, PA:N383D Increased virulence in ducks H5N1 1, 2, 3 1. Leung B. et al., 2010
2. Suttie A. et al., 2019
3. Xiao C. et al., 2016
PA:S224P, PA:N383D Increased virulence in mice H5N1 1, 2, 3 1. Leung B. et al., 2010
2. Suttie A. et al., 2019
3. Xiao C. et al., 2016
PA:K142R, PA:I147V, PA:I171V, PA:M182L Increased polymerase activity in mammalian cells H7N9 1, 2 1. Suttie A. et al., 2019
2. Schmolke M. et al., 2011
PA:V44I, PA:V127A, PA:C241Y, PA:A343T, PA:I573V Increased polymerase activity in mammalian cells H5N1 1, 2 1. Yamaji R. et al., 2015
2. Suttie A. et al., 2019
PA:V44I, PA:V127A, PA:C241Y, PA:A343T, PA:I573V Increased virulence in mice H5N1 1, 2 1. Yamaji R. et al., 2015
2. Suttie A. et al., 2019
PA:S149P, PA:H266R, PA:I357K, PA:S515T Increased polymerase activity in mammalian cells H5N1 1, 2 1. Leung B. et al., 2010
2. Suttie A. et al., 2019
PA:K356R, PB2:E627K Enhanced replication in mammalian cells H9N2 1, 2 1. Xu G. et al., 2016
2. Suttie A. et al., 2019
PA:K356R, PB2:E627K Increased polymerase activity in mammalian cells H9N2 1, 2 1. Xu G. et al., 2016
2. Suttie A. et al., 2019
PA:K356R, PB2:E627K Increased virulence in mice H9N2 1, 2 1. Xu G. et al., 2016
2. Suttie A. et al., 2019
HA1-5:D94N Increased pseudovirus binding to α2-6 H5N1 1, 2 1. Su Y. et al., 2008
2. Suttie A. et al., 2019
HA1-5:S121N Increased virus binding to α2-6 H5N1 1, 2 1. Suttie A. et al., 2019
2. Wang W. et al., 2010
HA1-5:S133A Increased pseudovirus binding to α2-6 H5N1 1, 2 1. Yang Z. et al., 2007
2. Suttie A. et al., 2019
HA1-5:A134V Decreased virus binding to α2-3 H5N1 1 1. Crusat M. et al., 2013
HA1-5:A134V Increased infectivity in mammalian cells H5N1 1, 2, 3 1. Naughtin M. et al., 2011
2. Suttie A. et al., 2019
3. Kongchanagul A. et al., 2008
HA1-5:A134V Increased virus binding to α2-6 H5N6 1 1. Peng X. et al., 2018
HA1-5:A134V Loss of binding to α2–3 H5N6 1 1. Peng X. et al., 2018
HA1-5:G139R Increased virus binding to α2-6 H5N1 1, 2 1. Suttie A. et al., 2019
2. Yamada S. et al., 2006
HA1-5:S154N Increased virus binding to α2-6 H5N1 1, 2 1. Suttie A. et al., 2019
2. Wang W. et al., 2010
HA1-5:N154D Decreased virus binding to α2-3 H7N9 1 1. Chang P. et al., 2023
HA1-5:N154D Decreased virus binding to α2-6 H7N9 1 1. Chang P. et al., 2023
HA1-5:N154D Enhanced replication in mammalian cells H7N9 1 1. Chang P. et al., 2023
HA1-5:N154D Decreased virulence in mice H9N2 1, 2 1. Jin F. et al., 2019
2. Suttie A. et al., 2019
HA1-5:S155N Increased virus binding to α2-6 H5N1 1, 2 1. Suttie A. et al., 2019
2. Wang W. et al., 2010
HA1-5:T156A Increased transmission in guinea pigs H5N1 1, 2, 3 1. Gao Y. et al., 2009
2. Suttie A. et al., 2019
3. Wang W. et al., 2010
HA1-5:T156A Increased virus binding to α2-6 H5N1 1, 2, 3 1. Gao Y. et al., 2009
2. Suttie A. et al., 2019
3. Wang W. et al., 2010
HA1-5:G182V Increased virus binding to α2-3 H7N9 1, 2 1. Dortmans J. et al., 2013
2. Suttie A. et al., 2019
HA1-5:N182K Increased virus binding to α2-6 H5N1 1, 2, 3, 4, 5 1. Gao Y. et al., 2009
2. Suttie A. et al., 2019
3. Wang W. et al., 2010
4. Yamada S. et al., 2006
5. Kongchanagul A. et al., 2008
HA1-5:N182D Increased virus binding to α2-6 H5N1 1, 2, 3, 4, 5 1. Gao Y. et al., 2009
2. Suttie A. et al., 2019
3. Wang W. et al., 2010
4. Yamada S. et al., 2006
5. Kongchanagul A. et al., 2008
HA1-5:V182N Decreased virus binding to α2-3 H13N6 1, 2 1. Suttie A. et al., 2019
2. Lu X. et al., 2013
HA1-5:V182N Increased virus binding to α2-6 H13N6 1, 2 1. Suttie A. et al., 2019
2. Lu X. et al., 2013
HA1-5:P182L Decreased virus binding to α2-3 H6N1 1, 2 1. Suttie A. et al., 2019
2. Wang F. et al., 2015
HA1-5:D183G Increased virus binding to α2-6 H5N1 1, 2 1. Chen L. et al., 2012
2. Suttie A. et al., 2019
HA1-5:E186G Decreased virulence in mice H5N1 1, 2, 3 1. Chen L. et al., 2012
2. Han P. et al., 2015
3. Suttie A. et al., 2019
HA1-5:E186G Increased virus binding to α2-6 H5N1 1, 2, 3 1. Chen L. et al., 2012
2. Han P. et al., 2015
3. Suttie A. et al., 2019
HA1-5:E186G Maintained virus binding to α2-3 H5N1 1, 2, 3 1. Chen L. et al., 2012
2. Han P. et al., 2015
3. Suttie A. et al., 2019
HA1-5:E186V Decreased virus binding to α2-3 H6N2 1, 2 1. Suttie A. et al., 2019
2. Qu Z. et al., 2017
HA1-5:T186V Enhanced binding affinity to mammalian cells H9N2 1, 2 1. Teng Q. et al., 2016
2. Suttie A. et al., 2019
HA1-5:T186V Enhanced replication in mammalian cells H9N2 1, 2 1. Teng Q. et al., 2016
2. Suttie A. et al., 2019
HA1-5:T186V Enhanced replication in mice H9N2 1, 2 1. Teng Q. et al., 2016
2. Suttie A. et al., 2019
HA1-5:T188I Increased pseudovirus binding to α2-6 H5N1 1, 2 1. Yang Z. et al., 2007
2. Suttie A. et al., 2019
HA1-5:K189R Increased virus binding to α2-6 H5N1 1, 2, 3 1. Suttie A. et al., 2019
2. Wang W. et al., 2010
3. Peng W. et al., 2018
HA1-5:K189T Increased virus binding to α2-6 H5N1 1, 2, 3 1. Suttie A. et al., 2019
2. Wang W. et al., 2010
3. Peng W. et al., 2018
HA1-5:Q192R Increased virus binding to α2-6 H5N1 1, 2, 3, 4 1. Chen L. et al., 2012
2. Suttie A. et al., 2019
3. Watanabe Y. et al., 2011
4. Yamada S. et al., 2006
HA1-5:Q192H Increased virus binding to α2-6 H5N1 1, 2, 3, 4 1. Chen L. et al., 2012
2. Suttie A. et al., 2019
3. Watanabe Y. et al., 2011
4. Yamada S. et al., 2006
HA1-5:N193K Increased virus binding to α2-6 H5N1 1, 2 1. Suttie A. et al., 2019
2. Yamada S. et al., 2006
HA1-5:V210I Increased virus binding to α2-6 H5N1 1, 2 1. Watanabe Y. et al., 2011
2. Suttie A. et al., 2019
HA1-5:G221D Increased virus binding to α2-6 H1N1 3
H6N1 1, 2		 1. Suttie A. et al., 2019
2. Vries R. et al., 2017
3. AbuBakar U. et al., 2023
HA1-5:Q222L Decreased virus binding to α2-3 H2N2 4
H5N1 1, 2
H3N2 3		 1. Chutinimitkul S. et al., 2010
2. Suttie A. et al., 2019
3. Song H. et al., 2017
4. AbuBakar U. et al., 2023
HA1-5:Q222L Increased virus binding to α2-6 H2N2 7
H6N2 2, 3, 6
H5N1 2, 8
H3N2 4
H4N6 2, 4
H9N2 1, 2, 5		 1. Wan H. et al., 2008
2. Suttie A. et al., 2019
3. Bosch F. et al., 1981
4. Song H. et al., 2017
5. Wan H. et al., 2007
6. Qu Z. et al., 2017
7. AbuBakar U. et al., 2023
8. Chutinimitkul S. et al., 2010
HA1-5:Q222L Transmitted via aerosol among guinea pigs H6N2 1, 2, 3 1. Suttie A. et al., 2019
2. Bosch F. et al., 1981
3. Qu Z. et al., 2017
HA1-5:Q222L Decreased virus binding to α2-6 H7N9 1, 2, 3 1. Xu R. et al., 2013
2. Suttie A. et al., 2019
3. Ramos I. et al., 2013
HA1-5:Q222L Increased virus binding to α2-3 H7N9 1, 2, 3 1. Xu R. et al., 2013
2. Suttie A. et al., 2019
3. Ramos I. et al., 2013
HA1-5:Q222L Loss of binding to α2–3 H10N8 (human isolate) 1, 2, 3, 4 1. Tzarum N. et al., 2017
2. Zhang H. et al., 2015
3. Suttie A. et al., 2019
4. Sang X. et al., 2015b
HA1-5:Q222L Enhanced contact transmission in ferrets H9N2 1, 2, 3 1. Wan H. et al., 2008
2. Suttie A. et al., 2019
3. Wan H. et al., 2007
HA1-5:Q222L Enhanced replication in ferrets H9N2 1, 2, 3 1. Wan H. et al., 2008
2. Suttie A. et al., 2019
3. Wan H. et al., 2007
HA1-5:Q222L Enhanced replication in mammalian cells H9N2 1, 2, 3 1. Wan H. et al., 2008
2. Suttie A. et al., 2019
3. Wan H. et al., 2007
HA1-5:L222I Decreased virus binding to α2-3 H7N9 1, 2 1. Xu R. et al., 2013
2. Suttie A. et al., 2019
HA1-5:S223N Increased virus binding to α2-6 H5N1 1, 2, 3, 4, 5, 6 1. Chutinimitkul S. et al., 2010
2. Suttie A. et al., 2019
3. Gambaryan A. et al., 2006
4. Shinya K. et al., 2010
5. Chen L. et al., 2012
6. Kongchanagul A. et al., 2008
HA1-5:G224A Dual receptor specificity H4N6 1, 2 1. Suttie A. et al., 2019
2. Song H. et al., 2017
HA1-5:G224A Increased virus binding to α2-6 H4N6 1, 2 1. Suttie A. et al., 2019
2. Song H. et al., 2017
HA1-5:G224S Increased virus binding to α2-6 H5N1 1, 2, 3, 5, 7
H4N6 3, 4
H6N6 6		 1. Wang F. et al., 2015
2. Stevens J. et al., 2006
3. Suttie A. et al., 2019
4. Song H. et al., 2017
5. Wang W. et al., 2010
6. Sun H. et al., 2017
7. Chutinimitkul S. et al., 2010
HA1-5:G224S Decreased virus binding to α2-3 H6N2 1, 5
H10N8 (human isolate) 1, 2, 4
H7N9 1, 3		 1. Suttie A. et al., 2019
2. Zhang H. et al., 2015
3. de Vries R. et al., 2017
4. Sang X. et al., 2015b
5. Qu Z. et al., 2017
HA1-5:G224S No binding to α2–6 H10N8 (human isolate) 1, 2, 3 1. Zhang H. et al., 2015
2. Suttie A. et al., 2019
3. Sang X. et al., 2015b
HA1-5:G224S Dual receptor specificity H4N6 1, 2 1. Suttie A. et al., 2019
2. Song H. et al., 2017
HA1-5:G224S Decreased virus binding to α2-6 H7N9 1, 2 1. Suttie A. et al., 2019
2. de Vries R. et al., 2017
HA1-5:G224S Increased replication in mammalian cells H1N2 1, 2 1. Suttie A. et al., 2019
2. Yu Z. et al., 2019
HA1-5:G224S Increased virulence in mice H1N2 1, 2 1. Suttie A. et al., 2019
2. Yu Z. et al., 2019
HA1-5:P235S Increased virus binding to α2-6 H5N1 1, 2 1. Watanabe Y. et al., 2011
2. Suttie A. et al., 2019
HA1-5:E251K Increased virus binding to α2-6 H5N1 1, 2 1. Chen L. et al., 2012
2. Suttie A. et al., 2019
HA2-5:K58I Decreased pH of fusion H5N1 1, 2, 3, 4 1. Reed M. et al., 2009
2. Abdelwhab E. et al., 2016
3. Krenn B. et al., 2011
4. Suttie A. et al., 2019
HA2-5:K58I Increased HA stability H5N1 1, 2, 3, 4 1. Reed M. et al., 2009
2. Abdelwhab E. et al., 2016
3. Krenn B. et al., 2011
4. Suttie A. et al., 2019
HA2-5:K58I Increased viral replication efficiency H5N1 1, 2, 3, 4 1. Reed M. et al., 2009
2. Abdelwhab E. et al., 2016
3. Krenn B. et al., 2011
4. Suttie A. et al., 2019
HA2-5:K58I Increased virulence in mice H5N1 1, 2, 3, 4 1. Reed M. et al., 2009
2. Abdelwhab E. et al., 2016
3. Krenn B. et al., 2011
4. Suttie A. et al., 2019
HA2-5:K64E Decreased HA stability H7N9 1, 2 1. Suttie A. et al., 2019
2. Sun X. et al., 2019
HA2-5:K64E Decreased virulence in mice H7N9 1, 2 1. Suttie A. et al., 2019
2. Sun X. et al., 2019
HA2-5:K64E Increased pH of fusion H7N9 1, 2 1. Suttie A. et al., 2019
2. Sun X. et al., 2019
HA1-5:E75K, HA1-5:S123P Increased virus binding to α2-6 H5N1 1, 2 1. Suttie A. et al., 2019
2. Yamada S. et al., 2006
HA1-5:E75K, HA1-5:S123P, HA2-5:R167K Increased virus binding to α2-6 H5N1 1, 2 1. Suttie A. et al., 2019
2. Yamada S. et al., 2006
HA1-5:E75K, HA1-5:S123P, HA1-5:N193K, HA2-5:R167K Increased virus binding to α2-6 H5N1 1, 2 1. Suttie A. et al., 2019
2. Yamada S. et al., 2006
HA1-5:E75K, HA1-5:N193K Increased virus binding to α2-6 H5N1 1, 2 1. Suttie A. et al., 2019
2. Yamada S. et al., 2006
HA1-5:E75K, HA1-5:N193K, HA2-5:R167K Increased virus binding to α2-6 H5N1 1, 2 1. Suttie A. et al., 2019
2. Yamada S. et al., 2006
HA1-5:E75K, HA2-5:R167K Increased virus binding to α2-6 H5N1 1, 2 1. Suttie A. et al., 2019
2. Yamada S. et al., 2006
HA1-5:H103Y, HA1-5:T156A, HA1-5:Q222L, HA1-5:G224S, PB2:E627K, PB1:H99Y Transmitted via aerosol among ferrets H5N1 1, 2, 3 1. Suttie A. et al., 2019
2. Herfst S. et al., 2012
3. Linster M. et al., 2014
HA1-5:S107R, HA1-5:T108I Increased pH of fusion H5N1 1, 2 1. Wessels U. et al., 2018
2. Suttie A. et al., 2019
HA1-5:S107R, HA1-5:T108I Increased virulence in chickens H5N1 1, 2 1. Wessels U. et al., 2018
2. Suttie A. et al., 2019
HA1-5:S107R, HA1-5:T108I Increased virulence in mice H5N1 1, 2 1. Wessels U. et al., 2018
2. Suttie A. et al., 2019
HA1-5:S123P, HA1-5:N193K Increased virus binding to α2-6 H5N1 1, 2 1. Suttie A. et al., 2019
2. Yamada S. et al., 2006
HA1-5:S123P, HA1-5:N193K, HA2-5:R167K Increased virus binding to α2-6 H5N1 1, 2 1. Suttie A. et al., 2019
2. Yamada S. et al., 2006
HA1-5:S133A, HA1-5:T188I Increased pseudovirus binding to α2-6 H5N1 1, 2 1. Yang Z. et al., 2007
2. Suttie A. et al., 2019
HA1-5:G139R, HA1-5:N182K Decreased virus binding to α2-3 H5N1 1, 2, 3 1. Chutinimitkul S. et al., 2010
2. Suttie A. et al., 2019
3. Yamada S. et al., 2006
HA1-5:G139R, HA1-5:N182K Increased virus binding to α2-6 H5N1 1, 2, 3 1. Chutinimitkul S. et al., 2010
2. Suttie A. et al., 2019
3. Yamada S. et al., 2006
HA1-5:N154D, HA1-5:N220K, HA1-5:Q222L, HA1-5:T315I Transmissible among ferrets H5N1 1, 2 1. Suttie A. et al., 2019
2. Imai M. et al., 2012
HA1-5:N154S, HA1-5:Q222L Increased virus binding to α2-6 H5N1 1, 2 1. Ilyushina N. et al., 2008
2. Suttie A. et al., 2019
HA1-5:N154S, HA1-5:Q222L, HA1-5:N244D Increased virus binding to α2-6 H5N1 1, 2 1. Ilyushina N. et al., 2008
2. Suttie A. et al., 2019
HA1-5:S155N, HA1-5:T156A Increased virus binding to α2-6 H5N1 1, 2, 3 1. Suttie A. et al., 2019
2. Wang W. et al., 2010
3. Wang F. et al., 2015
HA1-5:S155N, HA1-5:T156A, HA1-5:S223N Increased virus binding to α2-6 H5N1 1, 2 1. Suttie A. et al., 2019
2. Yen H. et al., 2009
HA1-5:S155N, HA1-5:T156A, HA1-5:S223N Reduced lethality in mice H5N1 1, 2 1. Suttie A. et al., 2019
2. Yen H. et al., 2009
HA1-5:S155N, HA1-5:T156A, HA1-5:S223N Systemic spread in mice H5N1 1, 2 1. Suttie A. et al., 2019
2. Yen H. et al., 2009
HA1-5:T156A, HA1-5:K189T, HA1-5:N220K, HA1-5:Q222L Increased virus binding to α2-6 H5N1 1, 2 1. Suttie A. et al., 2019
2. Peng W. et al., 2018
HA1-5:T156A, HA1-5:Q222L Increased virus binding to α2-6 H5N1 1, 2, 3 1. Suttie A. et al., 2019
2. Wang W. et al., 2010
3. Wang F. et al., 2015
HA1-5:T156A, HA1-5:Q222L, HA1-5:G224S Increased virus binding to α2-6 H5N1 1, 2, 3, 4 1. Suttie A. et al., 2019
2. Wang W. et al., 2010
3. Stevens J. et al., 2008
4. Wang F. et al., 2015
HA1-5:T156A, HA1-5:S223N Increased virus binding to α2-6 H5N1 1, 2, 3 1. Suttie A. et al., 2019
2. Wang W. et al., 2010
3. Wang F. et al., 2015
HA1-5:V182N, HA1-5:G224S Increased virus binding to α2-6 H7N9 1, 2 1. Suttie A. et al., 2019
2. de Vries R. et al., 2017
HA1-5:V182G, HA1-5:K189T, HA1-5:G224S Increased virus binding to α2-6 H7N9 1, 2 1. Suttie A. et al., 2019
2. de Vries R. et al., 2017
HA1-5:V182K, HA1-5:K189T, HA1-5:G224S Increased virus binding to α2-6 H7N9 1, 2 1. Suttie A. et al., 2019
2. de Vries R. et al., 2017
HA1-5:V182N, HA1-5:N220K, HA1-5:G224S Increased virus binding to α2-6 H7N9 1, 2 1. Suttie A. et al., 2019
2. de Vries R. et al., 2017
HA1-5:N182K, HA1-5:Q192R, HA1-5:Q222L, HA1-5:S223N, HA1-5:G224S Increased virus binding to α2-6 H5N1 1, 2 1. Chutinimitkul S. et al., 2010
2. Suttie A. et al., 2019
HA1-5:N182K, HA1-5:Q222L, HA1-5:S223N, HA1-5:G224S Increased virus binding to α2-6 H5N1 1, 2 1. Chutinimitkul S. et al., 2010
2. Suttie A. et al., 2019
HA1-5:E183G, HA1-5:E186D, HA1-5:K189S, HA1-5:Q222L, HA1-5:G224S Increased virus binding to α2-6 H5N1 1, 2 1. Suttie A. et al., 2019
2. Maines T. et al., 2011
HA1-5:E183G, HA1-5:Q222L, HA1-5:G224S Increased virus binding to α2-6 H5N1 1, 2 1. Chen L. et al., 2012
2. Suttie A. et al., 2019
HA1-5:D183G, HA1-5:S223N Increased virus binding to α2-6 H5N1 1, 2 1. Chen L. et al., 2012
2. Suttie A. et al., 2019
HA1-5:T185A, HA2-5:G193R Enhanced replication in ferrets H3N2 (human isolate) backbone with H9N2 HA 1, 2 1. Sorrell E. et al., 2009
2. Suttie A. et al., 2019
HA1-5:T185A, HA2-5:G193R Transmitted via aerosol among ferrets H3N2 (human isolate) backbone with H9N2 HA 1, 2 1. Sorrell E. et al., 2009
2. Suttie A. et al., 2019
HA1-5:E186G, HA1-5:Q222E, HA1-5:G224S Increased virus binding to α2-6 H5N1 1, 2 1. Chen L. et al., 2012
2. Suttie A. et al., 2019
HA1-5:K189R, HA1-5:Q222L, HA1-5:G224S Increased virus binding to α2-6 H5N1 1, 2, 3 1. Zhang H. et al., 2015
2. Suttie A. et al., 2019
3. Stevens J. et al., 2008
HA1-5:Q192R, HA1-5:Q222L, HA1-5:S223N, HA1-5:G224S Increased virus binding to α2-6 H5N1 1, 2 1. Chutinimitkul S. et al., 2010
2. Suttie A. et al., 2019
HA1-5:Q192R, HA1-5:Q222L, HA1-5:G224S Increased virus binding to α2-6 H5N1 1, 2, 3 1. Chen L. et al., 2012
2. Suttie A. et al., 2019
3. Chutinimitkul S. et al., 2010
HA1-5:Q192R, HA1-5:S223N Increased virus binding to α2-6 H5N1 1, 2, 3 1. Chen L. et al., 2012
2. Suttie A. et al., 2019
3. Chutinimitkul S. et al., 2010
HA1-5:N193K, HA2-5:R167K Increased virus binding to α2-6 H5N1 1, 2 1. Suttie A. et al., 2019
2. Yamada S. et al., 2006
HA1-5:K218Q, HA1-5:S223R Increased virus binding to α2-3 H5N1 1, 2 1. Guo H. et al., 2017
2. Suttie A. et al., 2019
HA1-5:K218Q, HA1-5:S223R Increased virus binding to α2-6 H5N1 1, 2 1. Guo H. et al., 2017
2. Suttie A. et al., 2019
HA1-5:N220K, HA1-5:G224S Increased virus binding to α2-6 H7N9 1, 2 1. Suttie A. et al., 2019
2. de Vries R. et al., 2017
HA1-5:Q222L, HA1-5:S223N, HA1-5:G224S Increased virus binding to α2-6 H5N1 1, 2 1. Chutinimitkul S. et al., 2010
2. Suttie A. et al., 2019
HA1-5:Q222L, HA1-5:G224S Decreased antiviral response in host H5N1 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 1. Gao Y. et al., 2009
2. Ayora-Talavera G. et al., 2009
3. Kode S. et al., 2019
4. Chutinimitkul S. et al., 2010
5. Wang F. et al., 2015
6. Stevens J. et al., 2006
7. Suttie A. et al., 2019
8. McCown M. et al., 2005
9. Stevens J. et al., 2008
10. Wang W. et al., 2010
11. Ilyushina N. et al., 2008
12. Chen L. et al., 2012
13. Harvey R. et al., 2004
14. Maines T. et al., 2011
HA1-5:Q222L, HA1-5:G224S Increased virus binding to α2-6 H5N1 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 14, 15, 16
H4N6 7, 12
H7N7 (human isolate) 7, 13		 1. Gao Y. et al., 2009
2. Ayora-Talavera G. et al., 2009
3. Kode S. et al., 2019
4. Chutinimitkul S. et al., 2010
5. Wang F. et al., 2015
6. Stevens J. et al., 2006
7. Suttie A. et al., 2019
8. McCown M. et al., 2005
9. Stevens J. et al., 2008
10. Wang W. et al., 2010
11. Ilyushina N. et al., 2008
12. Song H. et al., 2017
13. Srinivasan K. et al., 2013
14. Chen L. et al., 2012
15. Harvey R. et al., 2004
16. Maines T. et al., 2011
HA1-5:Q222L, HA1-5:G224S Reduced tissue tropism in guinea pigs H5N1 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 1. Gao Y. et al., 2009
2. Ayora-Talavera G. et al., 2009
3. Kode S. et al., 2019
4. Chutinimitkul S. et al., 2010
5. Wang F. et al., 2015
6. Stevens J. et al., 2006
7. Suttie A. et al., 2019
8. McCown M. et al., 2005
9. Stevens J. et al., 2008
10. Wang W. et al., 2010
11. Ilyushina N. et al., 2008
12. Chen L. et al., 2012
13. Harvey R. et al., 2004
14. Maines T. et al., 2011
HA1-5:Q222L, HA1-5:G224S Loss of binding to α2–3 H10N8 (human isolate) 1, 2, 3, 4 1. Tzarum N. et al., 2017
2. Zhang H. et al., 2015
3. Suttie A. et al., 2019
4. Sang X. et al., 2015b
HA1-5:Q222L, HA1-5:G224S No binding to α2–6 H10N8 (human isolate) 1, 2, 3, 4 1. Tzarum N. et al., 2017
2. Zhang H. et al., 2015
3. Suttie A. et al., 2019
4. Sang X. et al., 2015b
NA-1:V116A Reduced inhibition to Oseltamivir H5N1 1, 2 1. Hurt A. et al., 2007
2. Boltz D. et al., 2010
NA-1:V116A Reduced inhibition to Zanamiriv H5N1 1, 2 1. Hurt A. et al., 2007
2. Boltz D. et al., 2010
NA-1:V116A Reduced susceptibility to Oseltamivir H5N1 1, 2, 3 1. Hurt A. et al., 2007
2. Suttie A. et al., 2019
3. Boltz D. et al., 2010
NA-1:V116A Reduced susceptibility to Zanamivir H5N1 1, 2, 3 1. Hurt A. et al., 2007
2. Suttie A. et al., 2019
3. Boltz D. et al., 2010
NA-1:I117T Reduced inhibition to Oseltamivir H5N1 1 1. Kode S. et al., 2019
NA-1:I117T Reduced inhibition to Zanamiriv H5N1 1 1. Kode S. et al., 2019
NA-1:I117T Reduced susceptibility to Oseltamivir H5N1 1, 2 1. Kode S. et al., 2019
2. Suttie A. et al., 2019
NA-1:I117T Reduced susceptibility to Zanamivir H5N1 1, 2 1. Kode S. et al., 2019
2. Suttie A. et al., 2019
NA-1:E119A From normal to reduced inhibition to Oseltamivir H1N1 1, 2 1. Samson M. et al., 2014
2. Baek Y. et al., 2015
NA-1:E119A From normal to reduced inhibition to Peramivir H1N1 1, 2 1. Samson M. et al., 2014
2. Baek Y. et al., 2015
NA-1:E119A Highly reduced inhibition to Zanamivir H5N1 1, 2 1. Ilyushina N. et al., 2010
2. Baek Y. et al., 2015
NA-1:E119A Reduced inhibition to Laninamivir H1N1 1, 2 1. Samson M. et al., 2014
2. Baek Y. et al., 2015
NA-1:E119A Reduced inhibition to Oseltamivir H5N1 1, 2 1. Ilyushina N. et al., 2010
2. Baek Y. et al., 2015
NA-1:E119A Reduced inhibition to Zanamiriv H1N1 1, 2 1. Samson M. et al., 2014
2. Baek Y. et al., 2015
NA-1:E119A Reduced susceptibility to Oseltamivir H5N1 1, 2, 3 1. Ilyushina N. et al., 2010
2. Suttie A. et al., 2019
3. Baek Y. et al., 2015
NA-1:E119A Reduced susceptibility to Zanamivir H5N1 1, 2, 3 1. Ilyushina N. et al., 2010
2. Suttie A. et al., 2019
3. Baek Y. et al., 2015
NA-1:E119D Highly reduced inhibition to Laninamivir H1N1 1, 2, 3 1. Lloren K. et al., 2019
2. L’Huillier A. et al., 2015
3. Baek Y. et al., 2015
NA-1:E119D Highly reduced inhibition to Peramivir H1N1 1, 2, 3
H5N1 3		 1. Lloren K. et al., 2019
2. L’Huillier A. et al., 2015
3. Baek Y. et al., 2015
NA-1:E119D Highly reduced inhibition to Zanamivir H1N1 1, 2, 3
H5N1 3		 1. Lloren K. et al., 2019
2. L’Huillier A. et al., 2015
3. Baek Y. et al., 2015
NA-1:E119D Reduced inhibition to Oseltamivir H1N1 1, 2, 3
H5N1 3		 1. Lloren K. et al., 2019
2. L’Huillier A. et al., 2015
3. Baek Y. et al., 2015
NA-1:E119D Reduced susceptibility to Oseltamivir H5N1 1, 2 1. Suttie A. et al., 2019
2. Baek Y. et al., 2015
NA-1:E119D Reduced susceptibility to Peramivir H5N1 1, 2 1. Suttie A. et al., 2019
2. Baek Y. et al., 2015
NA-1:E119D Reduced susceptibility to Zanamivir H5N1 1, 2 1. Suttie A. et al., 2019
2. Baek Y. et al., 2015
NA-1:E119G From reduced to highly reduced inhibition to Peramivir H1N1 1, 3, 4, 5
H5N1 2, 4		 1. Lloren K. et al., 2019
2. Hurt A. et al., 2009
3. Pizzorno A. et al., 2011
4. Baek Y. et al., 2015
5. Tamura D. et al., 2015b
NA-1:E119G Highly reduced inhibition to Laninamivir H1N1 1, 2, 3, 4 1. Tamura D. et al., 2015b
2. Lloren K. et al., 2019
3. Pizzorno A. et al., 2011
4. Baek Y. et al., 2015
NA-1:E119G Highly reduced inhibition to Zanamivir H1N1 1, 3, 4, 5
H5N1 2, 4		 1. Lloren K. et al., 2019
2. Hurt A. et al., 2009
3. Pizzorno A. et al., 2011
4. Baek Y. et al., 2015
5. Tamura D. et al., 2015b
NA-1:E119G Reduced susceptibility to Peramivir H5N1 1, 2 1. Suttie A. et al., 2019
2. Baek Y. et al., 2015
NA-1:E119G Reduced susceptibility to Zanamivir H5N1 1, 2 1. Suttie A. et al., 2019
2. Baek Y. et al., 2015
NA-1:Q136L Highly reduced inhibition to Zanamivir H5N1 1 1. Hurt A. et al., 2010
NA-1:Q136L Reduced inhibition to Oseltamivir H5N1 1 1. Hurt A. et al., 2010
NA-1:Q136L Reduced susceptibility to Oseltamivir H5N1 1, 2 1. Suttie A. et al., 2019
2. Hurt A. et al., 2010
NA-1:Q136L Reduced susceptibility to Zanamivir H5N1 1, 2 1. Suttie A. et al., 2019
2. Hurt A. et al., 2010
NA-1:D199G Reduced inhibition to Oseltamivir H5N1 1 1. Hurt A. et al., 2009
NA-1:D199G Reduced inhibition to Zanamiriv H5N1 1 1. Hurt A. et al., 2009
NA-1:D199G Reduced susceptibility to Oseltamivir H5N1 1, 2 1. Suttie A. et al., 2019
2. Hurt A. et al., 2009
NA-1:D199G Reduced susceptibility to Zanamivir H5N1 1, 2 1. Suttie A. et al., 2019
2. Hurt A. et al., 2009
NA-1:I223M Reduced inhibition to Oseltamivir H5N1 1 1. Hurt A. et al., 2009
NA-1:I223M Reduced susceptibility to Oseltamivir H5N1 1, 2 1. Suttie A. et al., 2019
2. Hurt A. et al., 2009
NA-1:S247N Reduced inhibition to Oseltamivir H5N1 1 1. Boltz D. et al., 2010
NA-1:S247N Reduced susceptibility to Oseltamivir H5N1 1, 2 1. Suttie A. et al., 2019
2. Boltz D. et al., 2010
NA-1:H275Y From reduced to highly reduced inhibition to Oseltamivir H5N1 1, 2, 3, 4, 5 1. Hurt A. et al., 2009
2. Nguyen H. et al., 2013
3. Ilyushina N. et al., 2010
4. Baek Y. et al., 2015
5. Le Q. et al., 2005b
NA-1:H275Y From reduced to highly reduced inhibition to Peramivir H5N1 3, 4, 5, 7, 14
H1N1 1, 2, 6, 8, 9, 10, 11, 12, 13		 1. Okomo-Adhiambo M. et al., 2010b
2. Nguyen H. et al., 2012
3. Hurt A. et al., 2009
4. Nguyen H. et al., 2013
5. Ilyushina N. et al., 2010
6. Okomo-Adhiambo M. et al., 2013
7. Baek Y. et al., 2015
8. Leang S. et al., 2014
9. Ikematsu H. et al., 2012
10. Baz M. et al., 2009
11. Takashita E. et al., 2013
12. Dapat C. et al., 2013
13. Nguyen H. et al., 2010b
14. Le Q. et al., 2005b
NA-1:H275Y Reduced susceptibility to Oseltamivir H5N1 1, 2, 3, 4, 5, 6, 7 1. Hurt A. et al., 2009
2. Nguyen H. et al., 2013
3. Ilyushina N. et al., 2010
4. Suttie A. et al., 2019
5. Baek Y. et al., 2015
6. Gubareva L. et al., 2017b
7. Le Q. et al., 2005
NA-1:H275Y Reduced susceptibility to Peramivir H5N1 1, 2, 3, 4, 5, 6, 7 1. Hurt A. et al., 2009
2. Nguyen H. et al., 2013
3. Ilyushina N. et al., 2010
4. Suttie A. et al., 2019
5. Baek Y. et al., 2015
6. Gubareva L. et al., 2017b
7. Le Q. et al., 2005
NA-1:H275Y Highly reduced inhibition to Oseltamivir H1N1 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 1. Choi W. et al., 2013
2. Sheu T. et al., 2008
3. Okomo-Adhiambo M. et al., 2010b
4. Nguyen H. et al., 2012
5. Okomo-Adhiambo M. et al., 2013
6. Leang S. et al., 2014
7. Ikematsu H. et al., 2012
8. Baz M. et al., 2009
9. Takashita E. et al., 2013
10. Mishin V. et al., 2005
11. Dapat C. et al., 2013
12. Nguyen H. et al., 2010b
NA-1:H275Y Highly reduced inhibition to Peramivir H1N1 1, 2, 3, 4 1. Choi W. et al., 2013
2. Mishin V. et al., 2005
3. Okomo-Adhiambo M. et al., 2010b
4. Sheu T. et al., 2008
NA-1:E278Q Reduced susceptibility to Oseltamivir H5N1 1, 2 1. Govorkova E. et al., 2007
2. Suttie A. et al., 2019
NA-1:N295S From reduced to highly reduced inhibition to Oseltamivir H1N1 1, 3, 5, 6, 7, 8
H5N1 2, 4, 7, 9		 1. Choi W. et al., 2013
2. Earhart K. et al., 2009
3. Abed Y. et al., 2006
4. Ilyushina N. et al., 2010
5. Samson M. et al., 2014
6. Pizzorno A. et al., 2011
7. Baek Y. et al., 2015
8. Meijer A. et al., 2014
9. Le Q. et al., 2005b
NA-1:N295S Reduced inhibition to Peramivir H1N1 1, 2 1. Choi W. et al., 2013
2. Abed Y. et al., 2006
NA-1:N295S From normal to highly reduced inhibition to Peramivir H5N1 1, 2, 3, 4 1. Ilyushina N. et al., 2010
2. Earhart K. et al., 2009
3. Baek Y. et al., 2015
4. Le Q. et al., 2005b
NA-1:N295S From normal to reduced inhibition to Peramivir H1N1 1, 2, 3, 4 1. Samson M. et al., 2014
2. Meijer A. et al., 2014
3. Pizzorno A. et al., 2011
4. Baek Y. et al., 2015
NA-1:N295S From normal to reduced inhibition to Zanamivir H5N1 1, 2, 3, 4 1. Ilyushina N. et al., 2010
2. Earhart K. et al., 2009
3. Baek Y. et al., 2015
4. Le Q. et al., 2005b
NA-1:N295S Reduced susceptibility to Oseltamivir H5N1 1, 2, 3, 4, 5 1. Earhart K. et al., 2009
2. Ilyushina N. et al., 2010
3. Suttie A. et al., 2019
4. Baek Y. et al., 2015
5. Le Q. et al., 2005
NA-1:N295S Reduced susceptibility to Peramivir H5N1 1, 2, 3, 4, 5 1. Earhart K. et al., 2009
2. Ilyushina N. et al., 2010
3. Suttie A. et al., 2019
4. Baek Y. et al., 2015
5. Le Q. et al., 2005
NA-1:N295S Reduced susceptibility to Zanamivir H5N1 1, 2, 3, 4, 5 1. Earhart K. et al., 2009
2. Ilyushina N. et al., 2010
3. Suttie A. et al., 2019
4. Baek Y. et al., 2015
5. Le Q. et al., 2005
NA-1:K432T Reduced inhibition to Zanamiriv H5N1 1 1. Creanga A. et al., 2017
NA-1:K432T Reduced susceptibility to Zanamivir H5N1 1, 2 1. Suttie A. et al., 2019
2. Creanga A. et al., 2017
NA-1:I117V, NA-1:I314V Reduced inhibition to Oseltamivir H5N1 1 1. Hurt A. et al., 2007
NA-1:I117V, NA-1:I314V Reduced susceptibility to Oseltamivir H5N1 1, 2 1. Suttie A. et al., 2019
2. Hurt A. et al., 2007
NA-1:E119A, NA-1:H275Y Highly reduced inhibition to Oseltamivir H1N1 1
H5N1 1		 1. Baek Y. et al., 2015
NA-1:E119A, NA-1:H275Y Highly reduced inhibition to Peramivir H5N1 1 1. Baek Y. et al., 2015
NA-1:E119A, NA-1:H275Y Reduced inhibition to Zanamiriv H1N1 1
H5N1 1		 1. Baek Y. et al., 2015
NA-1:E119A, NA-1:H275Y Reduced susceptibility to Oseltamivir H5N1 1, 2 1. Suttie A. et al., 2019
2. Baek Y. et al., 2015
NA-1:E119A, NA-1:H275Y Reduced susceptibility to Peramivir H5N1 1, 2 1. Suttie A. et al., 2019
2. Baek Y. et al., 2015
NA-1:E119A, NA-1:H275Y Reduced susceptibility to Zanamivir H5N1 1, 2 1. Suttie A. et al., 2019
2. Baek Y. et al., 2015
NA-1:E119D, NA-1:H275Y Highly reduced inhibition to Laninamivir H1N1 1, 2 1. L’Huillier A. et al., 2015
2. Baek Y. et al., 2015
NA-1:E119D, NA-1:H275Y Highly reduced inhibition to Oseltamivir H1N1 1, 2
H5N1 2		 1. L’Huillier A. et al., 2015
2. Baek Y. et al., 2015
NA-1:E119D, NA-1:H275Y Highly reduced inhibition to Peramivir H1N1 1, 2
H5N1 2		 1. L’Huillier A. et al., 2015
2. Baek Y. et al., 2015
NA-1:E119D, NA-1:H275Y Highly reduced inhibition to Zanamivir H1N1 1, 2 1. L’Huillier A. et al., 2015
2. Baek Y. et al., 2015
NA-1:E119D, NA-1:H275Y Reduced inhibition to Zanamiriv H5N1 1 1. Baek Y. et al., 2015
NA-1:E119D, NA-1:H275Y Reduced susceptibility to Oseltamivir H5N1 1, 2 1. Suttie A. et al., 2019
2. Baek Y. et al., 2015
NA-1:E119D, NA-1:H275Y Reduced susceptibility to Peramivir H5N1 1, 2 1. Suttie A. et al., 2019
2. Baek Y. et al., 2015
NA-1:E119D, NA-1:H275Y Reduced susceptibility to Zanamivir H5N1 1, 2 1. Suttie A. et al., 2019
2. Baek Y. et al., 2015
NA-1:E119G, NA-1:H275Y Highly reduced inhibition to Laninamivir H1N1 1, 2 1. Tamura D. et al., 2015b
2. Baek Y. et al., 2015
NA-1:E119G, NA-1:H275Y Highly reduced inhibition to Oseltamivir H1N1 1, 2
H5N1 2		 1. Tamura D. et al., 2015b
2. Baek Y. et al., 2015
NA-1:E119G, NA-1:H275Y Highly reduced inhibition to Peramivir H1N1 1, 2
H5N1 2		 1. Tamura D. et al., 2015b
2. Baek Y. et al., 2015
NA-1:E119G, NA-1:H275Y Highly reduced inhibition to Zanamivir H1N1 1, 2 1. Tamura D. et al., 2015b
2. Baek Y. et al., 2015
NA-1:E119G, NA-1:H275Y Reduced inhibition to Zanamiriv H5N1 1 1. Baek Y. et al., 2015
NA-1:E119G, NA-1:H275Y Reduced susceptibility to Oseltamivir H5N1 1, 2 1. Suttie A. et al., 2019
2. Baek Y. et al., 2015
NA-1:E119G, NA-1:H275Y Reduced susceptibility to Peramivir H5N1 1, 2 1. Suttie A. et al., 2019
2. Baek Y. et al., 2015
NA-1:E119G, NA-1:H275Y Reduced susceptibility to Zanamivir H5N1 1, 2 1. Suttie A. et al., 2019
2. Baek Y. et al., 2015
NA-1:I223L, NA-1:S247N Reduced inhibition to Oseltamivir H5N1 1 1. Creanga A. et al., 2017
NA-1:I223L, NA-1:S247N Reduced susceptibility to Oseltamivir H5N1 1, 2 1. Suttie A. et al., 2019
2. Creanga A. et al., 2017
NA-1:I223M, NA-1:H275Y Highly reduced inhibition to Oseltamivir H1N1 1
H5N1 1		 1. Hurt A. et al., 2009
NA-1:I223M, NA-1:H275Y Highly reduced inhibition to Peramivir H1N1 1
H5N1 1		 1. Hurt A. et al., 2009
NA-1:I223M, NA-1:H275Y Reduced susceptibility to Oseltamivir H5N1 1, 2 1. Suttie A. et al., 2019
2. Hurt A. et al., 2009
NA-1:I223M, NA-1:H275Y Reduced susceptibility to Peramivir H5N1 1, 2 1. Suttie A. et al., 2019
2. Hurt A. et al., 2009
NA-1:I223V, NA-1:H275Y Highly reduced inhibition to Oseltamivir H1N1 1, 2, 3, 4
H5N1 4		 1. Choi W. et al., 2013
2. Centers for Disease Control and Prevention, 2009(2009
3. Pizzorno A. et al., 2011
4. Hurt A. et al., 2009
NA-1:I223V, NA-1:H275Y Highly reduced inhibition to Peramivir H1N1 1, 2, 3, 4
H5N1 4		 1. Choi W. et al., 2013
2. Centers for Disease Control and Prevention, 2009(2009
3. Pizzorno A. et al., 2011
4. Hurt A. et al., 2009
NA-1:I223V, NA-1:H275Y Reduced susceptibility to Oseltamivir H5N1 1, 2 1. Suttie A. et al., 2019
2. Hurt A. et al., 2009
NA-1:I223V, NA-1:H275Y Reduced susceptibility to Peramivir H5N1 1, 2 1. Suttie A. et al., 2019
2. Hurt A. et al., 2009
NA-1:K150N, NA-1:I223L, NA-1:S247N Reduced inhibition to Oseltamivir H5N1 1 1. Boltz D. et al., 2010
NA-1:K150N, NA-1:I223L, NA-1:S247N Reduced susceptibility to Oseltamivir H5N1 1, 2 1. Suttie A. et al., 2019
2. Boltz D. et al., 2010
HA1-5:K189T, HA1-5:G224S Dual α2–3 and α2–6 binding H7N9 1, 2 1. Suttie A. et al., 2019
2. de Vries R. et al., 2017
NP:E434K, HA1-5:Q223P, HA2-5:D46E Enhanced contact transmission in guinea pigs H9N2 1, 2 1. Suttie A. et al., 2019
2. Sang X. et al., 2015b
NP:E434K, HA1-5:Q223P, PB2:D195N Enhanced contact transmission in guinea pigs H9N2 1, 2 1. Suttie A. et al., 2019
2. Sang X. et al., 2015b
NA-1:S110F Reduced inhibition to Oseltamivir H1N1 1, 2 1. Lackenby A. et al., 2018
2. Huang W. et al., 2018
NA-1:S110F Reduced inhibition to Zanamiriv H1N1 1, 2 1. Lackenby A. et al., 2018
2. Huang W. et al., 2018
NA-1:I117R Reduced inhibition to Zanamiriv H1N1 1 1. Gubareva L. et al., 2017
NA-1:E119V From reduced to highly reduced inhibition to Oseltamivir H1N1 1, 2 1. Choi W. et al., 2013
2. Abed Y. et al., 2006
NA-1:E119V Highly reduced inhibition to Peramivir H1N1 1, 2 1. Choi W. et al., 2013
2. Abed Y. et al., 2006
NA-1:E119V Highly reduced inhibition to Zanamivir H1N1 1, 2, 3 1. Choi W. et al., 2013
2. Abed Y. et al., 2006
3. Pizzorno A. et al., 2011
NA-1:E119V Reduced inhibition to Oseltamivir H1N1 1 1. Pizzorno A. et al., 2011
NA-1:E119V Reduced inhibition to Peramivir H1N1 1 1. Pizzorno A. et al., 2011
NA-1:Q136K Highly reduced inhibition to Peramivir H1N1 1, 2, 3 1. Samson M. et al., 2014
2. Pizzorno A. et al., 2013
3. Kaminski M. et al., 2013
NA-1:Q136K Highly reduced inhibition to Zanamivir H1N1 1, 2, 3 1. Samson M. et al., 2014
2. Pizzorno A. et al., 2013
3. Kaminski M. et al., 2013
NA-1:Q136K Reduced inhibition to Laninamivir H1N1 1, 2, 3 1. Samson M. et al., 2014
2. Pizzorno A. et al., 2013
3. Kaminski M. et al., 2013
NA-1:R152K From normal to reduced inhibition to Zanamivir H1N1 1, 2 1. Lloren K. et al., 2019
2. Baek Y. et al., 2015
NA-1:R152K Reduced inhibition to Laninamivir H1N1 1, 2 1. Lloren K. et al., 2019
2. Baek Y. et al., 2015
NA-1:R152K Reduced inhibition to Oseltamivir H1N1 1, 2 1. Lloren K. et al., 2019
2. Baek Y. et al., 2015
NA-1:Y155H Highly reduced inhibition to Oseltamivir H1N1 1 1. Monto A. et al., 2006
NA-1:Y155H Highly reduced inhibition to Zanamivir H1N1 1 1. Monto A. et al., 2006
NA-1:D199E Reduced inhibition to Oseltamivir H1N1 1, 2 1. Lloren K. et al., 2019
2. Takashita E. et al., 2015
NA-1:D199Y Reduced inhibition to Oseltamivir H1N1 1 1. Takashita E. et al., 2020
NA-1:D199Y Reduced inhibition to Zanamiriv H1N1 1 1. Takashita E. et al., 2020
NA-1:I223K Reduced inhibition to Oseltamivir H1N1 1, 2, 3 1. Nguyen H. et al., 2010
2. Huang L. et al., 2014
3. Takashita E. et al., 2015
NA-1:I223L Reduced inhibition to Oseltamivir H1N1 1 1. Govorkova E. et al., 2022
NA-1:I223R From normal to reduced inhibition to Zanamivir H1N1 1, 2, 3, 4, 5 1. van der Vries E. et al., 2010
2. Takashita E. et al., 2015
3. Huang L. et al., 2014
4. Eshaghi A. et al., 2011
5. Pizzorno A. et al., 2012
NA-1:I223R Reduced inhibition to Oseltamivir H1N1 1, 2, 3, 4, 5 1. van der Vries E. et al., 2010
2. Takashita E. et al., 2015
3. Huang L. et al., 2014
4. Eshaghi A. et al., 2011
5. Pizzorno A. et al., 2012
NA-1:I223T From normal to reduced inhibition to Oseltamivir H1N1 1 1. Samson M. et al., 2014
NA-1:S247G Reduced inhibition to Oseltamivir H1N1 1 1. Takashita E. et al., 2015
NA-1:S247R From reduced to highly reduced inhibition to Laninamivir H1N1 1 1. Gubareva L. et al., 2017
NA-1:S247R From reduced to highly reduced inhibition to Peramivir H1N1 1 1. Gubareva L. et al., 2017
NA-1:S247R Reduced inhibition to Oseltamivir H1N1 1 1. Gubareva L. et al., 2017
NA-1:S247R Reduced inhibition to Zanamiriv H1N1 1 1. Gubareva L. et al., 2017
NA-1:R293K Reduced inhibition to Oseltamivir H1N1 1, 2 1. Tamura D. et al., 2015b
2. Baek Y. et al., 2015
NA-1:R293K Reduced inhibition to Zanamiriv H1N1 1 1. Choi W. et al., 2013
NA-1:I427T Reduced inhibition to Laninamivir H1N1 1 1. Takashita E. et al., 2020
NA-1:I427T Reduced inhibition to Oseltamivir H1N1 1 1. Takashita E. et al., 2020
NA-1:I427T Reduced inhibition to Zanamiriv H1N1 1 1. Takashita E. et al., 2020
NA-1:I436N Reduced inhibition to Laninamivir A(H1N1)pdm09 1 1. Kwon J. et al., 2018
NA-1:I436N Reduced inhibition to Oseltamivir A(H1N1)pdm09 1 1. Kwon J. et al., 2018
NA-1:I436N Reduced inhibition to Peramivir A(H1N1)pdm09 1 1. Kwon J. et al., 2018
NA-1:I436N Reduced inhibition to Zanamiriv A(H1N1)pdm09 1 1. Kwon J. et al., 2018
NA-1:P458T Highly reduced inhibition to Laninamivir H1N1 1 1. Lloren K. et al., 2019
NA-1:P458T Highly reduced inhibition to Oseltamivir H1N1 1 1. Lloren K. et al., 2019
NA-1:P458T Highly reduced inhibition to Peramivir H1N1 1 1. Lloren K. et al., 2019
NA-1:P458T Highly reduced inhibition to Zanamivir H1N1 1 1. Lloren K. et al., 2019
NA-1:I117V, NA-1:E119V Highly reduced inhibition to Zanamivir H1N1 1 1. Choi W. et al., 2013
NA-1:I117M, NA-1:E119V Highly reduced inhibition to Zanamivir H1N1 1 1. Choi W. et al., 2013
NA-1:I117M, NA-1:E119V Reduced inhibition to Oseltamivir H1N1 1 1. Choi W. et al., 2013
NA-1:I117V, NA-1:H275Y Highly reduced inhibition to Oseltamivir H1N1 1 1. Choi W. et al., 2013
NA-1:I117M, NA-1:H275Y Highly reduced inhibition to Oseltamivir H1N1 1 1. Choi W. et al., 2013
NA-1:I117V, NA-1:N295S Reduced inhibition to Oseltamivir H1N1 1 1. Choi W. et al., 2013
NA-1:I117M, NA-1:N295S Reduced inhibition to Oseltamivir H1N1 1 1. Choi W. et al., 2013
NA-1:E119V, NA-1:H275Y Highly reduced inhibition to Zanamivir H1N1 1 1. Choi W. et al., 2013
NA-1:E119V, NA-1:H275Y Reduced inhibition to Oseltamivir H1N1 1 1. Choi W. et al., 2013
NA-1:Q136K, NA-1:D151E Reduced inhibition to Peramivir H1N1 1 1. Okomo-Adhiambo M. et al., 2010b
NA-1:Q136K, NA-1:D151E Reduced inhibition to Zanamiriv H1N1 1 1. Okomo-Adhiambo M. et al., 2010b
NA-1:Q136K, NA-1:H275Y Highly reduced inhibition to Oseltamivir H1N1 1 1. Okomo-Adhiambo M. et al., 2010b
NA-1:Q136K, NA-1:H275Y Highly reduced inhibition to Peramivir H1N1 1 1. Okomo-Adhiambo M. et al., 2010b
NA-1:Q136K, NA-1:H275Y Reduced inhibition to Zanamiriv H1N1 1 1. Okomo-Adhiambo M. et al., 2010b
NA-1:G147R, NA-1:H275Y Highly reduced inhibition to Oseltamivir H1N1 1 1. Gubareva L. et al., 2017
NA-1:G147R, NA-1:H275Y Highly reduced inhibition to Peramivir H1N1 1 1. Gubareva L. et al., 2017
NA-1:D151E, NA-1:H275Y From reduced to highly reduced inhibition to Peramivir H1N1 1 1. Okomo-Adhiambo M. et al., 2010b
NA-1:D151E, NA-1:H275Y Highly reduced inhibition to Oseltamivir H1N1 1 1. Okomo-Adhiambo M. et al., 2010b
NA-1:D151N, NA-1:H275Y From reduced to highly reduced inhibition to Peramivir H1N1 1 1. Okomo-Adhiambo M. et al., 2010b
NA-1:D151N, NA-1:H275Y Highly reduced inhibition to Oseltamivir H1N1 1 1. Okomo-Adhiambo M. et al., 2010b
NA-1:D151G, NA-1:H275Y Highly reduced inhibition to Oseltamivir H1N1 1 1. Okomo-Adhiambo M. et al., 2010b
NA-1:D151G, NA-1:H275Y Highly reduced inhibition to Peramivir H1N1 1 1. Okomo-Adhiambo M. et al., 2010b
NA-1:D151G, NA-1:H275Y Reduced inhibition to Zanamiriv H1N1 1 1. Okomo-Adhiambo M. et al., 2010b
NA-1:D199N, NA-1:H275Y Highly reduced inhibition to Oseltamivir H1N1 1 1. Okomo-Adhiambo M. et al., 2013
NA-1:D199N, NA-1:H275Y Highly reduced inhibition to Peramivir H1N1 1 1. Okomo-Adhiambo M. et al., 2013
NA-1:I223V, NA-1:N295S Reduced inhibition to Oseltamivir H1N1 1 1. Choi W. et al., 2013
NA-1:I223K, NA-1:H275Y Highly reduced inhibition to Oseltamivir H1N1 1 1. Nguyen H. et al., 2012
NA-1:I223K, NA-1:H275Y Highly reduced inhibition to Peramivir H1N1 1 1. Nguyen H. et al., 2012
NA-1:I223K, NA-1:H275Y Reduced inhibition to Laninamivir H1N1 1 1. Nguyen H. et al., 2012
NA-1:I223K, NA-1:H275Y Reduced inhibition to Zanamiriv H1N1 1 1. Nguyen H. et al., 2012
NA-1:I223R, NA-1:H275Y Highly reduced inhibition to Oseltamivir H1N1 1, 2, 3 1. Nguyen H. et al., 2010
2. Pizzorno A. et al., 2012
3. Nguyen H. et al., 2012
NA-1:I223R, NA-1:H275Y Highly reduced inhibition to Peramivir H1N1 1, 2, 3 1. Nguyen H. et al., 2010
2. Pizzorno A. et al., 2012
3. Nguyen H. et al., 2012
NA-1:I223R, NA-1:H275Y Reduced inhibition to Laninamivir H1N1 1, 2, 3 1. Nguyen H. et al., 2010
2. Pizzorno A. et al., 2012
3. Nguyen H. et al., 2012
NA-1:I223R, NA-1:H275Y Reduced inhibition to Zanamiriv H1N1 1, 2, 3 1. Nguyen H. et al., 2010
2. Pizzorno A. et al., 2012
3. Nguyen H. et al., 2012
NA-1:S247N, NA-1:H275Y Highly reduced inhibition to Oseltamivir H1N1 1 1. Hurt A. et al., 2011
NA-1:S247N, NA-1:H275Y Highly reduced inhibition to Peramivir H1N1 1 1. Hurt A. et al., 2011
NA-1:H275Y, NA-1:I436N Highly reduced inhibition to Oseltamivir A(H1N1)pdm09 1 1. Kwon J. et al., 2018
NA-1:H275Y, NA-1:I436N Highly reduced inhibition to Peramivir A(H1N1)pdm09 1 1. Kwon J. et al., 2018
NA-1:H275Y, NA-1:I436N Reduced inhibition to Laninamivir A(H1N1)pdm09 1 1. Kwon J. et al., 2018
NA-1:H275Y, NA-1:I436N Reduced inhibition to Zanamiriv A(H1N1)pdm09 1 1. Kwon J. et al., 2018
NA-1:R293K, NA-1:H275Y Highly reduced inhibition to Oseltamivir H1N1 1 1. Choi W. et al., 2013
NA-1:N295S, NA-1:H275Y Highly reduced inhibition to Oseltamivir H1N1 1 1. Choi W. et al., 2013
NA-1:Q313K, NA-1:I427T From normal to reduced inhibition to Zanamivir H1N1 1, 2 1. Okomo-Adhiambo M. et al., 2010b
2. Hurt A. et al., 2012
NA-1:Q313K, NA-1:I427T Reduced inhibition to Oseltamivir H1N1 1, 2 1. Okomo-Adhiambo M. et al., 2010b
2. Hurt A. et al., 2012
NA-1:S334N, NA-1:H275Y Highly reduced inhibition to Oseltamivir H1N1 1 1. Choi W. et al., 2013
NA-1:I117V, NA-1:N295S, NA-1:H275Y Highly reduced inhibition to Oseltamivir H1N1 1 1. Choi W. et al., 2013
NA-1:I117V, NA-1:N295S, NA-1:H275Y Reduced inhibition to Zanamiriv H1N1 1 1. Choi W. et al., 2013
NA-1:I117M, NA-1:N295S, NA-1:H275Y Highly reduced inhibition to Oseltamivir H1N1 1 1. Choi W. et al., 2013
NA-1:I117M, NA-1:N295S, NA-1:H275Y Reduced inhibition to Zanamiriv H1N1 1 1. Choi W. et al., 2013
NA-1:Q136K, NA-1:D151N, NA-1:H275Y Highly reduced inhibition to Oseltamivir H1N1 1 1. Okomo-Adhiambo M. et al., 2010b
NA-1:Q136K, NA-1:D151N, NA-1:H275Y Highly reduced inhibition to Peramivir H1N1 1 1. Okomo-Adhiambo M. et al., 2010b
NA-1:I223V, NA-1:N295S, NA-1:H275Y Highly reduced inhibition to Oseltamivir H1N1 1 1. Choi W. et al., 2013
NA-1:I223V, NA-1:N295S, NA-1:H275Y Reduced inhibition to Zanamiriv H1N1 1 1. Choi W. et al., 2013
PB1:K229R Resistance to Favipiravir Unknown 1 1. Komeno T. et al., 2022
PA:E23G PA inhibitor (PAI) baloxavir susceptibility A(H1N1)pdm09 1, 2, 3, 4 1. Govorkova E. et al., 2022
2. Jones J. et al., 2022
3. Gubareva L., 2019
4. Takashita E. et al., 2020
PA:E23K PA inhibitor (PAI) baloxavir susceptibility A(H1N1)pdm09 1, 2, 3, 4 1. Govorkova E. et al., 2022
2. Jones J. et al., 2022
3. Omoto S. et al., 2018
4. Takashita E. et al., 2020b
PA:E23R PA inhibitor (PAI) baloxavir susceptibility A(H1N1)pdm09 1 1. Jones J. et al., 2022b
PA:K34R PA inhibitor (PAI) baloxavir susceptibility A(H1N1)pdm09 1 1. Govorkova E. et al., 2022
PA:A36V PA inhibitor (PAI) baloxavir susceptibility A(H1N1) 1 1. Omoto S. et al., 2018
PA:A37T PA inhibitor (PAI) baloxavir susceptibility A(H1N1)pdm09 1 1. Sato M. et al., 2021
PA:I38F PA inhibitor (PAI) baloxavir susceptibility A(H1N1)pdm09 1, 2, 3 1. Omoto S. et al., 2018
2. Jones J. et al., 2020
3. Koszalka P. et al., 2019
PA:I38L PA inhibitor (PAI) baloxavir susceptibility A(H1N1)pdm09 1, 2, 3, 4, 5 1. Takashita E. et al., 2020
2. Chesnokov A. et al., 2019
3. Gubareva L., 2019
4. Hickerson B. et al., 2022
5. Hashimoto T. et al., 2021
PA:I38M PA inhibitor (PAI) baloxavir susceptibility A(H1N1)pdm09 1, 2, 3, 4 1. Omoto S. et al., 2018
2. Jones J. et al., 2020
3. Kiso M. et al., 2020
4. Koszalka P. et al., 2019
PA:I38N PA inhibitor (PAI) baloxavir susceptibility A(H1N1) 1, 2 1. Ince W. et al., 2020
2. Hashimoto T. et al., 2021
PA:I38S PA inhibitor (PAI) baloxavir susceptibility A(H1N1)pdm09 1, 2, 3, 4, 5 1. Chesnokov A. et al., 2019
2. Govorkova E. et al., 2022
3. Takashita E. et al., 2020b
4. Hashimoto T. et al., 2021
5. Sato M. et al., 2020
PA:I38T PA inhibitor (PAI) baloxavir susceptibility A(H1N1)pdm09 1, 2, 3, 4, 5, 7, 8, 9, 10
H1N1 6		 1. Koszalka P. et al., 2019
2. Chesnokov A. et al., 2019
3. Imai M. et al., 2019
4. Takashita E. et al., 2018
5. Noshi T. et al., 2018
6. Govorkova E. et al., 2022
7. Omoto S. et al., 2018
8. Takashita E. et al., 2020b
9. Checkmahomed L. et al., 2020
10. Jones J. et al., 2020
PA:I38V PA inhibitor (PAI) baloxavir susceptibility H1N1 1
A(H1N1)pdm09 2, 3		 1. Govorkova E. et al., 2022
2. Gubareva L., 2019
3. Omoto S. et al., 2018
PA:E119D PA inhibitor (PAI) baloxavir susceptibility A(H1N1) 1 1. Omoto S. et al., 2018
PA:E198K PA inhibitor (PAI) baloxavir susceptibility A(H1N1)pdm09 1 1. Takizawa N. et al., 2022
PA:E199G PA inhibitor (PAI) baloxavir susceptibility A(H1N1)pdm09 1, 2 1. Govorkova E. et al., 2022
2. Kiso M. et al., 2020
PA:E199D PA inhibitor (PAI) baloxavir susceptibility A(H1N1)pdm09 1 1. Hickerson B. et al., 2022
NP:Y52N Evade human BTN3A3 (inhibitor of avian influenza A viruses replication) Unknown 1 1. Pinto R. et al., 2023
NP:F313Y Evade human BTN3A3 (inhibitor of avian influenza A viruses replication) Unknown 1 1. Pinto R. et al., 2023
NP:F313V Evade human BTN3A3 (inhibitor of avian influenza A viruses replication) Unknown 1 1. Pinto R. et al., 2023
NA-1:S364N Distruption of the second sialic acid binding site (2SBS) Unknown 1 1. Uhlendorff J. et al., 2009
NA-1:S369C Distruption of the second sialic acid binding site (2SBS) Unknown 1 1. Du W. et al., 2018
NA-1:T397A Distruption of the second sialic acid binding site (2SBS) Unknown 1 1. Dai M. et al., 2017
M2:V27I Conferred Amantidine resistance Unknown 1 1. Lee J. et al., 2008
NA-1:A369I Distruption of the second sialic acid binding site (2SBS) Unknown 1
H5N1 2		 1. Du W. et al., 2018
2. de Vries E. et al., 2023
NA-1:K432E Distruption of the second sialic acid binding site (2SBS) Unknown 1 1. Dai M. et al., 2021
NA-1:K432N Distruption of the second sialic acid binding site (2SBS) Unknown 1 1. Dai M. et al., 2021
NA-1:Q136R Highly reduced inhibition to Peramivir Unknown 1 1. Meijer A. et al., 2014
NA-1:Q136R Highly reduced inhibition to Zanamivir Unknown 1 1. Meijer A. et al., 2014
NA-1:Q136R Reduced inhibition to Laninamivir Unknown 1 1. Meijer A. et al., 2014
NP:R99K, NP:S345N, HA1-5:H103Y, HA1-5:T156A, HA1-5:Q222L, HA1-5:G224S, PB2:E627K, PB1:H99Y, PB1:I368V Transmitted via aerosol among ferrets H5N1 1, 2 1. Suttie A. et al., 2019
2. Herfst S. et al., 2012
HA1-5:S123P, HA2-5:R167K Increased virus binding to α2-6 H5N1 1, 2 1. Suttie A. et al., 2019
2. Yamada S. et al., 2006
HA1-5:L129V, HA1-5:A134V Increased virus binding to α2-6 H5N1 1, 2 1. Auewarakul P. et al., 2007
2. Suttie A. et al., 2019
HA1-5:N182K, HA1-5:Q222L, HA1-5:G224S Increased virus binding to α2-6 H5N1 1, 2 1. Chutinimitkul S. et al., 2010
2. Suttie A. et al., 2019
NA-1:I222K Reduced susceptibility to Laninamivir H7N9 1 1. Nilsson B. et al., 2017
NA-1:I222K Reduced susceptibility to Oseltamivir H7N9 1 1. Nilsson B. et al., 2017
NA-1:I222K Reduced susceptibility to Peramivir H7N9 1 1. Nilsson B. et al., 2017
NA-1:I222K Reduced susceptibility to Zanamivir H7N9 1 1. Nilsson B. et al., 2017
NA-1:E276D Reduced susceptibility to Laninamivir H7N9 1 1. Nilsson B. et al., 2017
NA-1:E276D Reduced susceptibility to Oseltamivir H7N9 1 1. Nilsson B. et al., 2017
NA-1:E276D Reduced susceptibility to Peramivir H7N9 1 1. Nilsson B. et al., 2017
NA-1:E276D Reduced susceptibility to Zanamivir H7N9 1 1. Nilsson B. et al., 2017
NA-1:R292K Reduced susceptibility to Zanamivir H4N2 1
H7N9 2, 3		 1. Bogs J. et al., 2011
2. Nilsson B. et al., 2017
3. Krenn B. et al., 2011
NA-1:R292K Reduced susceptibility to Laninamivir H7N9 1, 2 1. Nilsson B. et al., 2017
2. Krenn B. et al., 2011
NA-1:R292K Reduced susceptibility to Oseltamivir H7N9 1, 2 1. Nilsson B. et al., 2017
2. Krenn B. et al., 2011
NA-1:R292K Reduced susceptibility to Peramivir H7N9 1, 2 1. Nilsson B. et al., 2017
2. Krenn B. et al., 2011
NA-1:R371K Reduced susceptibility to Laninamivir H7N9 1 1. Nilsson B. et al., 2017
NA-1:R371K Reduced susceptibility to Oseltamivir H7N9 1 1. Nilsson B. et al., 2017
NA-1:R371K Reduced susceptibility to Peramivir H7N9 1 1. Nilsson B. et al., 2017
NA-1:R371K Reduced susceptibility to Zanamivir H7N9 1 1. Nilsson B. et al., 2017
NA-1:E119V, NA-1:E222V Reduced susceptibility to Oseltamivir H7N9 1 1. Soubies S. et al., 2010
NA-1:I396M Distruption of the second sialic acid binding site (2SBS) H5N1 1 1. de Vries E. et al., 2023
NA-1:I396V Distruption of the second sialic acid binding site (2SBS) H5N1 1 1. de Vries E. et al., 2023
PB2:M631L Increased polymerase activity in mice H10N7 1 1. Zhang X. et al., 2017
PB2:M631L Increased virulence in mice H10N7 1 1. Zhang X. et al., 2017
NP:L283P, NP:F313Y, NP:R100I Resistance to human interferon-induced antiviral factor MxA H5N1 1 1. Mänz B. et al., 2013b
NP:L283P, NP:F313V, NP:R100I Resistance to human interferon-induced antiviral factor MxA H5N1 1 1. Mänz B. et al., 2013b
NP:L283P, NP:F313Y, NP:R100V Resistance to human interferon-induced antiviral factor MxA H5N1 1 1. Mänz B. et al., 2013b
NP:F313V, NP:L283P, NP:R100V Resistance to human interferon-induced antiviral factor MxA H5N1 1 1. Mänz B. et al., 2013b
HA1-5:N189D Increased virus binding to α2-6 H5N1 1 1. Jang S. et al., 2024
HA1-5:N189D Transmissible among ferrets H5N1 1 1. Jang S. et al., 2024
HA1-5:T134A Increased viral replication in mice lungs H9N2 1 1. Zhang J. et al., 2023
HA1-5:T134A Increased virus thermostability H9N2 1 1. Zhang J. et al., 2023
HA1-5:R152Q Increased replication in avian cells H9N2 1 1. Zhang J. et al., 2023
HA1-5:R152Q Increased viral replication in mammalian cells H9N2 1 1. Zhang J. et al., 2023
HA1-5:R152Q Increased virus thermostability H9N2 1 1. Zhang J. et al., 2023
HA1-5:T183P, HA1-5:M223L Contact transmission in guinea pigs H9N2 1 1. Liu K. et al., 2023
HA1-5:T183P, HA1-5:M223L Enhanced replication in mice H9N2 1 1. Liu K. et al., 2023
HA1-5:T183P, HA1-5:M223L Enhanced virulence in mice H9N2 1 1. Liu K. et al., 2023
HA1-5:T183P, HA1-5:M223L Increased virus binding to α2-6 H9N2 1 1. Liu K. et al., 2023
HA1-5:N193D Contact transmission in ferrets H5N1 1 1. Jang S. et al., 2024
HA1-5:N193D Increased virulence in mice H5N1 1 1. Jang S. et al., 2024
HA1-5:N193D Increased virus binding to α2-6 H5N1 1 1. Jang S. et al., 2024
HA1-5:N194D, HA1-5:A223E, NS-1:A53D Increased virulence in mice H1N1 1 1. Zhu M. et al., 2023
HA1-5:I208T Increased replication in avian cells H9N2 1 1. Zhang J. et al., 2023
HA1-5:I208T Increased replication in mammalian cells H9N2 1 1. Zhang J. et al., 2023
HA1-5:I208T Increased viral replication in mice lungs H9N2 1 1. Zhang J. et al., 2023
HA1-5:H152N, HA1-5:S260R, PA:I38M Increased virulence in mice H6N6 1 1. Tan L. et al., 2014
HA1-5:A156V Decreased virulence in mice H7N2 1 1. Lyashko A. et al., 2023
HA1-5:A156V Increased virus binding to α2-6 H7N2 1 1. Lyashko A. et al., 2023
HA1-5:A103V Decreased pH of fusion H6N2 1 1. Tang S. et al., 2024
HA1-5:A103V, PB2:E627K Decreased pH of fusion H6N2 1 1. Tang S. et al., 2024
HA1-5:A103V, PB2:E627K Enhanced replication in guinea pigs H6N2 1 1. Tang S. et al., 2024
HA1-5:A103V, PB2:E627K Increased replication in mammalian cells H6N2 1 1. Tang S. et al., 2024
HA1-5:A103V, PB2:E627K Increased virulence in mice H6N2 1 1. Tang S. et al., 2024
HA1-5:R189M, HA1-5:Q222L, HA1-5:G224S Increased virus binding to α2-6 H5N1 1 1. Eggink D. et al., 2020
HA1-5:L190P Increased virus binding to α2-3 H3N2 1, 2 1. Liang W. et al., 2022
2. Hu M. et al., 2023
HA1-5:L190P Prevents airborne transmission in ferrets H3N2 1 1. Hu M. et al., 2023
HA1-5:S205Y Increased virus binding to α2-6 H3N1 1 1. Suzuki Y. et al., 1989
HA1-5:N220K, HA1-5:Q222L Increased virus binding to α2-6 H5N1 1, 2 1. Eggink D. et al., 2020
2. Imai M. et al., 2012
HA1-5:N220K, HA1-5:Q222L Decreased virus binding to α2-3 H5N1 1 1. Imai M. et al., 2012
PB2:Q591R Increased polymerase activity in mammalian cells H5N1 1, 2 1. Cauldwell A. et al., 2013
2. Peacock T. et al., 2023
PB2:K702R Increased polymerase activity in avian cells H5N1 1 1. Peacock T. et al., 2023
PB2:K702R Increased polymerase activity in mammalian cells H5N1 1 1. Peacock T. et al., 2023
PB2:D740N Increased polymerase activity in avian cells H5N1 1 1. Peacock T. et al., 2023
PB2:D740N Increased polymerase activity in mammalian cells H5N1 1 1. Peacock T. et al., 2023
PB2:T588I Enhanced polymerase activity H1N1 1 1. Zhao Z. et al., 2014
PB2:T588I Enhanced virulence in mice H1N1 1 1. Zhao Z. et al., 2014
PB2:Q591R, PB2:G590S Increased polymerase activity in mammalian cells H1N1 1 1. Mehle A. et al., 2009
PB2:Q591R, PB2:G590S Increased viral replication in mammalian cells H1N1 1 1. Mehle A. et al., 2009
PB2:K699R Enhanced virulence in mice H1N1 1 1. Zhang T. et al., 2017
PB2:K699R Increased viral replication in mammalian cells H1N1 1 1. Zhang T. et al., 2017
PA:D347G, PA:S49Y, PB2:S155N Increased polymerase activity in mammalian cells H9N2 1 1. Guo Y. et al., 2023
PA:D347G, PA:S49Y, PB2:S155N Increased viral replication in mammalian cells H9N2 1 1. Guo Y. et al., 2023
PA:D347G, PA:S49Y, PB2:S155N Increased virulence in mice H9N2 1 1. Guo Y. et al., 2023
PB2:A655V, PB2:E543D, PB2:K526R, PB2:E627V Enhanced pathogenicity in mice H9N2 1 1. Arai Y. et al., 2019
PB2:A655V, PB2:E543D, PB2:K526R, PB2:E627V Increased polymerase activity in mammalian cells H9N2 1 1. Arai Y. et al., 2019
NP:V284M, M1:R211Q, M1:R95K, PB2:T81I, HA1-5:K301R, PB2:E627K Transmitted via aerosol among ferrets H7N1 1 1. Sutton T. et al., 2014
PB2:M483K Increased replication in mammalian cells H7N9 1 1. Chan M. et al., 2020
PB2:F323L Increased replication in mammalian cells H3N2 1 1. Choi E. et al., 2020
PB2:F323L Increased viral replication in mice lungs H3N2 1 1. Choi E. et al., 2020
PB1:H115Q, PB2:E627K Transmitted via aerosol among guinea pigs H7N9 1 1. Zhang C. et al., 2021
HA1-5:T195I Increased binding breadth to glycans bearing terminal α2-3 sialic acids H5N1 1 1. Good M. et al., 2024
PA:S225E Enhanced replication in mammalian cells H5N1 1 1. Zhang M. et al., 2025
PA:S225E Enhanced replication in mice H5N1 1 1. Zhang M. et al., 2025
PA:S225E Enhanced virulence in mice H5N1 1 1. Zhang M. et al., 2025
PA:S225E Increased replication in avian cells H5N1 1 1. Zhang M. et al., 2025