Table 3. Mutations in the conserved motifs I – IV of the PB1 protein and their effects on replicative ability in human and chicken cells.
Motif | Mutation(s) | Mutant BHG polymerase activity (%)1 | Virus(es) possessing the respective mutation(s) | |
Human cells | Chicken cells | |||
T303I | 27.2 | 53.9 | A/chicken/Taiwan/G2/87 (H6N1)A/duck/HK/412/78 (H4N2) | |
I | T303S | 78.9 | 88.8 | A/Guangxi/1/05 (H5N1) |
N306T | 2.4 | 0.8 | A/Thailand/271/05 (H1N1) | |
II | M409T | 0 | 0.2 | A/swine/Nordkirchen/IDT1993/03 (H3N2) |
D439E | 49.0 | 34.2 | A/bar-headed goose/Qinghai/1/05 (H5N1)A/whooper swan/Qinghai/01/05 (H5N1) | |
Q442L | 19.2 | 6.2 | A/duck/Vietnam/8/05 (H5N1)A/duck/Vietnam/GZ-8/05 (H5N1)A/Hong Kong/483/97 (H5N1) | |
Q442R/D445E/F447L | 0 | 0.3 | A/duck/Hubei/wq/03 (H5N1) | |
S444P | 0 | 0.4 | A/chicken/Anhui/1089/07 (H5N1) | |
III | D445G | 0 | 0.5 | A/mallard/Yan chen/05 (H4N6) |
D445S/D446S | 0 | 0.3 | A/swine/Doetlingen/IDT4735/2005 (H1N2) | |
D445C/F447V/L449I | 0 | 0.3 | A/chicken/Shantou/1126/01 (H9N2) | |
D446N | 0 | 0.3 | A/chicken/Guangdong/5/97 (H9N2)A/chicken/Guangdong/10/00 (H9N2)A/chicken/Jiangsu/1/00 (H9N2) | |
A448V | 40.8 | 96.9 | A/swine/Shanghai/1/07 (H1N2)A/swine/North Carolina/93523/01 (H1N2) | |
I475V | 67.6 | 73.1 | A/Indonesia/CDC292N/05 (H5N1)A/Queensland/60/05 (H3N2)A/chicken/Taiwan/2838N/00 (H6N1) | |
N476Y | 0 | 0.3 | A/swine/Anhui/ca/04 (H5N1) | |
N476D | 0 | 0.3 | A/Indonesia/286H/06 (H5N1)A/chicken/Taiwan/G2/87 (H6N1) | |
IV | N476L/M477T | 0 | 0.4 | A/great black-headed gull/Qinghai/2/05 (H5N1) |
N476T/S478T | 0 | 0.3 | Four 2005 H5N1 (Qinghai-Lake) isolates2 | |
S478T | 0 | 0.3 | Four 2005 H5N1 (Qinghai-Lake) isolates2 | |
S478R | 0 | 0.2 | A/swine/Guangxi/wz/04 (H5N1) | |
K480R | 117.2 | 113.1 | Several pandemic (2009) H1N1 viruses; several swine viruses | |
K481E | 0 | 0.3 | A/duck/Hunan/3340/06 (H5N1) | |
K481T | 0 | 0.2 | A/chicken/Hong Kong/873.3/01 (H5N1) | |
K481N | 0 | 0.3 | A/turkey/Israel/1567/04 (H9N2) | |
Y483H | 0.5 | 0.3 | A/swine/Korea/S83/04 (H9N2) |
The indicated mutations were introduced into the PB1 protein of A/bar-headed goose/Qinghai/1/2005 (H5N1; BHG) virus. Polymerase activity in human 293T and avian DF-1 cells is indicated as percentage relative to wild-type PB1 activity.
For some of these isolates, different sequences are reported in the Los Alamos National Laboratory and NIH NCBI databases.