Table 2.
Key genetic mutations in individual viral proteins of 2013 H7N9 and 1997 H5N1 influenza viruses
| Importance of the mutation |
2013 influenza A H7N9 |
1997 influenza A H5N1 |
|||
|---|---|---|---|---|---|
| Human | Avian and environmental | Human | Avian and environmental | ||
| Haemagglutinin (H3 numbering) | |||||
| Ala135Thr | Increased viral replication | ND | ND | ND | ND |
| Asn158Asp | Mammalian transmission | ND | ND | ND | ND |
| Asn224Lys | Mammalian transmission | ND | ND | ND | ND |
| Gly228Ser | Mammalian transmission | ND | ND | ND | ND |
| Thr318Ile | Mammalian transmission | ND | ND | ND | ND |
| Ser138Ala | Ser variant associated with adaptation to pigs | 9/10 | All | All | All |
| Thr160Ala | Increased binding to α-2,6-linked sialic acid receptor | All | All | 3 of 5 | 6 of 10 |
| Gly186Val | Increased binding to α-2,6-linked sialic acid receptor | 9 of 10 | All | ND | ND |
| Gln226Leu | Increased binding to α-2,6-linked sialic acid receptor | 8 of 10* | 5 of 6 | ND | ND |
| Multibasic aminoacid at HA0 cleavage site | Cleavage by ubiquitous proteases | ND | ND | All | All |
| Neuraminidase (viral release from host cell surface) | |||||
| Deletions in stalk region | Increased virulence | All | All | All | All |
| Arg292Lys | Neuraminidase resistance | 2 of 11 | ND | ND | ND |
| PB2 (viral replication) | |||||
| Leu89Val | Enhanced polymerase activity | All | All | All | All |
| Glu627Lys | Improved viral replication at 33°C | 7 of 9 | ND | 2 of 9 | ND |
| Asp701Asn | Mammalian adaptation | 1 of 9 | ND | ND | ND |
| PB1 (viral replication) | |||||
| His99Tyr | Enables droplet transmission in ferrets | ND | ND | ND | ND |
| Ile368Val | Enables droplet transmission in ferrets | 5 of 7 | All | ND | ND |
| PB1-F2 (induce cellular apoptosis and inhibit function of type I interferon) | |||||
| Full-length | Full-length PB1-F2 needed for virulence in mice | All | 3 of 4 | All | All |
| Asn66Ser | Increased virulence in a mice model | ND | ND | ND | ND |
| Matrix protein M1 (viral assembly and budding) | |||||
| Asn30Asp, Thr215Ala | Increased virulence in a mice model | All | All | All | All |
| Matrix protein M2 | |||||
| Ser31Asn | Amantadine resistance | All | All | ND | ND |
| NS1 (counteracts host antiviral response) | |||||
| Pro42Ser | Increased virulence in mice | All | All | All | All |
| PDZ-binding motif | Signalling of host proteins | Deleted | Deleted | Avian type | Avian type |
Aminoacid sequences of A/Zhejiang/DTID-ZJU01/2013(H7N9), A/Hangzhou/1/2013(H7N9), A/Hangzhou/2/2013(H7N9), A/Hangzhou/3/2013(H7N9), A/Shanghai/4664T/2013(H7N9), A/Nanjing/1/2013(H7N9), A/Fujian/1/2013, A/Taiwan/S02076/2013(H7N9), A/chicken/Zhejiang/DTID-ZJU01/2013(H7N9), A/environment/Hangzhou/34/2013(H7N9), A/environment/Nanjing/2913/2013(H7N9), and all 1997 influenza A H5N1 strains were obtained from NCBI Influenza Virus Resource or from 11, 12, 29, 35, 44. Aminoacid sequences of 2013 influenza A H7N9 sequences of human isolates from Shanghai or Anhui were obtained from Global Initiative on Sharing Avian Influenza Data (GISAID) database and 12, 35 or both. Aminoacid substitutions of avian and environmental strains from Shanghai were obtained from reference 35. The appendix shows details of sequences deposited into GISAID database. Only strains with full-length sequence at the time of writing were included. Duplicate strain names but different sequences were excluded from the analysis. ND=not detected.
Gln226Ile was present in A/Hangzhou/1/2013(H7N9).