Table 1.
Mutations with a described biological effect identified in the European HPAI A(H5Nx) viruses, 2020–2022.
| Effect | Protein | Mutation | N. viruses | N. viruses from mammals | References |
|---|---|---|---|---|---|
| Enhance polymerase activity and replication in mammals or mammalian cells | PB2 | D253N | 1 | – | (Zhang et al. 2018) |
| T271A | 1 | 1 | (Bussey et al. 2010) | ||
| I292V | 798 | – | (Gao et al. 2019) | ||
| K389R | All/almost all viruses (N = 1,637) | (Hu et al. 2017b) | |||
| K482R | 19 | 3 | (Yamayoshi et al. 2018, Yamayoshi et al. 2014) | ||
| K526R | 4 | – | (Song et al. 2014) | ||
| A588V | 4 | – | (Xiao et al. 2016) | ||
| V598T/I | All/almost all viruses (N = 1,945) | (Hu et al. 2017b) | |||
| E627K | 32 | 18 | (Bortz et al. 2011; Fornek et al. 2009; Hatta et al. 2001, Hatta et al. 2007; Herfst et al. 2012; Kim et al. 2010; Manzoor et al. 2009; Richard et al. 2017; Shinya et al. 2004) | ||
| D701N | 6 | 4 | (Gao et al. 2009; Le et al. 2009; Li et al. 2005; Steel et al. 2009; Taft et al. 2015) | ||
| PA | V63I | 16 | 1 | (Hu et al. 2017a, Hu et al. 2016) | |
| T97I | 2 | – | (Taft et al. 2015) | ||
| K158R | 7 | – | (Elgendy et al. 2017) | ||
| K356R | 3 | – | (Xu et al. 2016) | ||
| K497R | 118 | – | (Yamayoshi et al. 2018) | ||
| NP | I41V | 29 | 3 | (Zhu et al. 2015) | |
| N319K | 36 | 5 | (Gabriel, Herwig, and Klenk 2008, Gabriel et al. 2005) | ||
| NS1 | I106M | All/almost all viruses (N = 1,954) | (Ayllon et al. 2014) | ||
| C138F | All/almost all viruses (N = 1,943) | (Li et al. 2018) | |||
| In vitro increase binding to human-type receptors alpha2,6-SA | HAa | D94N (D101N) | 6 | – | (Su et al. 2008) |
| S133A (S137A) | All/almost all viruses (N = 1,952) | (Yang et al. 2007) | |||
| S154N (S158N) | All/almost all viruses (N = 1,931) | (Wang et al. 2010) | |||
| S155N (S159N) | 5 | – | (Wang et al. 2010) | ||
| T156A (T160A) | All/almost all viruses (N = 1,939) | (Gao et al. 2009; Wang et al. 2010) | |||
| T188I (T192I) | 1 | – | (Yang et al. 2007) | ||
| V210I (V214I) | 3 | – | (Watanabe et al. 2011) | ||
| E251K (E255K) | 7 | – | (Chen et al. 2012) | ||
| S123P-496K (S128P-R496K (HA2-R167K)) | 4 | – | (Yamada et al. 2006) | ||
| Increase virulence in mice | PB2 | D9N | 2 | – | (Kim et al. 2010) |
| NS1 | P42S | All/almost all viruses (N = 1,922) | (Jiao et al. 2008) | ||
| L103F, I106M | All/almost all viruses (N = 1,919) | (Kuo and Krug 2009; Spesock et al. 2011) | |||
| 227ESEV230 (PDZ domain) | 1,115 | – | (Jackson et al. 2008; Soubies et al. 2010) | ||
| Enhance replication in mammalian cells, decrease IF response | NS1 | K55E, K66E, C138F | 1,087 | – | (Li et al. 2018) |
| Resistance toward antiviral drugs: $ Oseltamivir and/or Zanamivir § Laninamivir # Baloxavir ^ Amantidine-Rimantidine |
NAb | I117T$ | 1 | – | (Kode et al. 2019) |
| I117V$ | 2 | – | (Adams et al. 2019) | ||
| R152K§ | 1 | – | (Gubareva et al. 2017) | ||
| I223T$ | 1 | – | (Samson et al. 2014) | ||
| S247R$ | 1 | – | (Gubareva et al. 2017) | ||
| S247N$ | 5 | – | (Hurt et al. 2011) | ||
| PA | 34R# | 1 | – | (Govorkova et al. 2022) | |
| 199G# | 5 | – | (Govorkova et al. 2022; Kiso et al. 2020) | ||
| M2 | V27A^ | 4 | – | (Abed, Goyette, and Boivin 2005; Cheung et al. 2006; Ilyushina, Govorkova, and Webster 2005; Lan et al. 2010) | |
| V27I^ | 1 | – | (Chizhmakov et al. 2003) | ||
| A30S^ | 1 | – | (Cheung et al. 2006; Ilyushina, Govorkova, and Webster 2005) | ||
| S31N^ | 7 | – | (Buranathai et al. 2007; Cheung et al. 2006; He et al. 2008; Ilyushina, Govorkova, and Webster 2005; Lan et al. 2010; Puthavathana et al. 2005) | ||
| Decrease antiviral response in ferrets | NS1 | N205S (with NS2: T47A) | 1,112 | – | (Imai et al. 2010) |
| Disruption of the second sialic acid binding site (2SBS) | NAb | S369I | 44 | – | (Du et al. 2021, Du et al. 2018) |
| S369C/N/R | 3 | – | (Du et al. 2021, Du et al. 2018) | ||
| K432E/N | 38 | – | (Du et al. 2021, Du et al. 2018) | ||
| Evasion human BTN3A3 | NP | Y52N | 43 | 1 | (Pinto et al. 2023, Pinto et al. 2022) |
| Adaptation to domestic birds/increased virulence | NA | 22-AA deletion in the NA stalk region | 7 | – | (Hoffmann et al. 2012; Munier et al. 2010; Sorrell et al. 2010; Zhou et al. 2009) |
a
H5 numbering (H3 numbering).
b
N1 numbering.