Table 2.
Genetic changes of internal genes of influenza virus affecting interspecies transmission
| Protein | Effect of viral gene mutations that facilitate interspecies transmission | Host protein implicated in host restriction | Mutations responsible for interspecies jumping |
|---|---|---|---|
| PB2 | Improve polymerase activity and RNA replication in recipient species [11] Binding to the host protein importin necessary for the transport of PB2 into the nucleus [97] |
Importin [97] | 591K: avian-to-human adaptation of H5N1 virus [98] 627K: avian-to-human adaptation for H5N1and H7N9 viruses 11, 12 701N: avian-to-human adaptation for H5N1 [11], H7N9 [12], and H7N7 viruses [99]; avian to seal adaptation for H3N8 virus [65] Ability to bind importin-α7: avian-to-human adaptation [97] |
| PA | Improve polymerase activity and RNA replication in recipient species [100] | N/A | 552S: avian-to-human adaptation [100] |
| PB1-F2 | Improve polymerase activity and RNA replication in recipient species [101] | N/A | Truncated form of PB1-F2: avian-to-human and avian-to-swine adaptation [102] |
| PA-X | Changes in inflammatory, apoptotic, and T-lymphocyte signaling pathway [103] | N/A | Truncated form of PA-X: avian to human, swine, and canine and equine adaptation [103] |
| PA-N182 | Avian viruses may lack this protein [104]; however, its function is currently not known | N/A | Non-AUG codon at position 182: found mainly in avian and swine H9N2 virus [104] |
| Nucleoprotein | Binding to the host protein importin is necessary for the transport of viral nucleoprotein into the nucleus [97] Differential susceptibility to the host antiviral protein MxA [105] |
Importin [97] MxA [105] |
Nucleoprotein from 2009 pandemic H1N1 virus: avian-to-human adaptation [105] |
| NS1 | Binding to TRIM25, NS1 blocks RIG-I ubiquitination and type I IFN production in recipient species [106] | TRIM25 [106] | NS1 from 2009 pandemic H1N1 virus: avian-to-human adaptation [106] |
| NS2 (or NEP) | Improve polymerase activity and RNA replication in recipient species [107] | N/A | M16I: avian-to-human adaptation for H5N1 virus [107] |
Abbreviations: MxA = myxovirus resistance gene A; TRIM25 = tripartite motif 25.