Table 4.
Experimentally verified molecular markers/motifs in the polymerase basic protein 1 (PB1; segment 2) gene of influenza virus associated with polymerase activity, replication, virulence, and transmissibility
| Protein | Mutation/motif | Phenotype | Subtypes tested | References |
|---|---|---|---|---|
| PB1 | D3Va | Increased polymerase activity and viral replication in avian and mammalian cell lines | H5N1 | [301] |
| N105S | Increase polymerase activity and replication in mammalian cell line, increased virulence in mice | H5N1 | [117] | |
| K207R | Decreased polymerase activity in mammalian cell line | H5N1 | [302] | |
| Y436H | Decreased polymerase activity in mammalian cell line; decreased virulence in ducks, ferrets and mice | H5N1 | [302] | |
| V473L | Decreased polymerase activity and replication efficiency in mammalian cells | H1N1 with PB2, PB1, PA NP from H5N1 | [303] | |
| K577E | Increased polymerase activity and virulence in mice | H9N2 | [118] | |
| V598P | Decreased polymerase activity and replication efficiency in mammalian cells | H1N1 with PB2, PB1, PA NP from H5N1 | [303] | |
| D622G | Increased polymerase activity and virulence in mice | H5N1 | [304] | |
| T677M | Increased polymerase activity in mammalian cell line, decreased replication efficiency, decreased virulence in mice | H5N1 | [72] | |
| S678N | Increased replication in avian and mammalian cell lines | H7N7 | [124] | |
| V3A, N328K, N375S | Decreased replication efficiency and virulence in ferrets | H5N1 | [93] | |
| V473L, P598L | Decreased polymerase activity and replication in mammalian cells | H1N1 with PB2, PB1, PA NP from H5N1 | [303] | |
| H99Y (with HA: H110Y, T160A, G226L, G228S; PB2: E627K) | Airborne transmissible in ferrets | H5N1 | [15, 58] | |
| PB1-F2 | N66S | Enhanced replication, virulence and antiviral response in mice | H5N1 | [171, 305] |
| T51M, V56A, E87G | Decrease polymerase activity, replication and virulence in ducks | H5N1 | [173] |
Single mutations are presented first followed by motifs involving multiple mutations. Individual markers and motifs are listed in numerical order for ease of identifying mutation of interest
aMutations/motifs in both PB1 and PB1-F2 proteins are numbered according to alignments with A/Goose/Guangdong/1/1996 (H5N1)