Table 1.
Summary of influenza virus variants and mutations that affect replication and virulence in mice
| Protein | Virus | Mouse | Mutation | Effect | Reference(s) |
|---|---|---|---|---|---|
| HA | A/Vietnam/1203/2004(H5N1) | BALB/c | Deletion of polybasic cleavage site | Reduced respiratory and systemic replication. Reduced proinflammatory cytokines in lungs | Suguitan et al. (2012) |
| A/Hong Kong/156/97(H5N1) | ddY | P211T | Decreased virulence | Hiromoto et al. (2000) | |
| Reassortant WSN-HA + A/Hong Kong/1/68(H1N1xH3N2) | BALB/c | T160N, P162S | Increased virulence | Keleta et al. (2008) | |
| A/Aichi/2/68(H3N2) | BALB/c | G218E | Increased virulence | Narasaraju et al. (2009) | |
| A/Mallard duck/Pennsylvania/10218/84(H5N2) | S203F, E273G, L320P | Adaptation and virulence | Smirnov et al. (2000) | ||
| A/California/04/09(H1N1pdm09), A/Tennessee/1-560/09(H1N1pdm09) | BALB/c | D222G | Mouse adaptation and virulence | Ilyushina et al. (2010) | |
| A/Brisbane/59/2007(H1N1) | BALB/c | T89I, N125T, D221G | Mouse adaptation and virulence | Xu et al. (2011a) | |
| A/Hamburg/04/09(H1N1pdm09) | BALB/c | D222G K163E | Mouse adaptation and pathogenicity | Seyer et al. (2012) | |
| A/Hong Kong/1/68(H3N2) | CD-1 | G218W | Mouse adaptation and virulence | Ping et al. (2010) | |
| A/Hong Kong/1/68(H3N2) | CD-1 | T156N | Mouse adaptation and virulence | Ping et al. (2010) | |
| Reassortant WSN-HA + A/Hong Kong/1/68(H1N1xH3N2) | BALB/c | N154S | Mouse adaptation | Keleta et al. (2008) | |
| A/Vietnam/1203/2004(H5N1) NS1-deleted | Outbred | K58I | Increased immunogenicity | Krenn et al. (2011) | |
| A/black duck/New Jersey/1580/78(H2N3) | E216D, K307R, T318I | Mice adaptation and virulence | Govorkova et al. (2000) | ||
| A/JapanxBellamy/57(H2N1) | K25T, S203F | ||||
| M1 | A/black duck/New Jersey/1580/78(H2N3) | N30D, Q214H | Mice adaptation and virulence | Govorkova et al. (2000) | |
| A/JapanxBellamy/57(H2N1) | M179K | ||||
| A/Wisconsin/33 | A41V + T139A | Mice adaptation neurovirulence | Ward (1995) | ||
| A/FM/1/47(H1N1) | T139A | Mice adaptation and virulence | Brown and Bailly (1999) | ||
| A/duck/Guangxi/53/2002(H5N1) | BALB/c | N30D + T215A | Increased virulence | Fan et al. (2009) | |
| M2 | A/black duck/New Jersey/1580/78(H2N3), A/JapanxBellamy/57(H2N1) | N93S | Mice adaptation and virulence | Govorkova et al. (2000) | |
| NS1 | Reassortant A/Hong Kong/1/68(H3N2) x PR8 | BALB/c | F103L + M106I | Increased infectivity and virulence | Dankar et al. (2011) |
| A/Puerto Rico/8/34(H1N1) | PKR KO, IFNAR/IL28R KO | R184G | Increased replication in mice lungs | Steidle et al. (2010) | |
| A/Aichi/2/68(H3N2) | BALB/c | D125G | Increased virulence | Narasaraju et al. (2009) | |
| A/Hong Kong/156/97(H5N1) | ddY | D101N | Increased virulence | Hiromoto et al. (2000) | |
| A/Duck/Guangxi/12/03(H5N1) | BALB/c | P42S | Increased virulence | Jiao et al. (2008) | |
| A/Duck/Guangxi/27/03(H5N1) | BALB/c | S42P | Attenuation | ||
| A/Duck/Shandong/093/2004(H5N1) | BALB/c | E92D | Decreased virulence | Long et al. (2008) | |
| PA | A/Hong Kong/156/97(H5N1) | ddY | G631S | Increased virulence | Hiromoto et al. (2000) |
| A/Hamburg/04/09(H1N1pdm09) | BALB/c | F35L | Mouse adaptation and pathogenicity | Seyer et al. (2012) | |
| PB1 | A/Hong Kong/156/97(H5N1) | ddY | H456Y, S712P | Increased virulence | Hiromoto et al. (2000) |
| A/Cambodia/P0322095/2005(H5N1) | BALB/c | 473L + 598L | Decrease in mouse infectivity | Xu et al. (2012) | |
| A/Wisconsin/33(H1N1) PB2K627E | BALB/c | L473V + L598P | Restore mouse infection/replication | ||
| Reassortant A/California/07/2009(H1N1pdm09) + WSN | BALB/c | 473L | Decrease in mouse infectivity | ||
| PB1-F2 | A/Viet Nam/1203/2004(H5N1) | C57BL/6/A | N66S | Increased virulence | Schmolke et al. (2011) |
| No effect | |||||
| Reassortant A/WSN/33(H1N1) + A/HK/156/97(H5N1) PB1, A/Brevig Mission/1918(H1N1) | C57BL/6 | N66S | Increased virulence | Conenello et al. (2007) | |
| Reassortant A/Puerto Rico/8/34(H1N1) + A/Wuhan/359/95(H3N2) PB1 | DBA/2 | P62L + H75R + S82L | Increased virulence | Alymova et al. (2011) | |
| A/Puerto Rico/8/34 (H1N1) | BALB/c | I68T + L69Q + V70G | Reduced primary viral infectivity and secondary bacterial pneumonia | Alymova et al. (2014) | |
| PB2 | A/Hong Kong/1/68(H3N2) | CD-1 | K482R, D701N, D740N | Increased mouse virulence | Ping et al. (2011) |
| A/Hong Kong/1/68 (H3N2) | CD-1 | D701N | Mouse adaptation and virulence | Ping et al. (2010) | |
| A/Hong Kong/156/97(H5N1) | ddY | N701D | Increased virulence | Hiromoto et al. (2000) | |
| A/Seal/Massachussetts/1/80(H7N7) | BALB/c | D701N | Increased virulence | Gabriel et al. (2005) | |
| A/duck/Guangxi/22/2001(H5N1) | BALB/c | D701N | Adaptation and increased virulence | Li et al. (2005) | |
| A/New York/1682/2009(H1N1pdm09) | BALB/c | D701N | Increased virulence | Zhou et al. (2013) | |
| A/chicken/Netherlands/621557/03(H7N7) | BALB/c | E627K | Mouse adaptation and increased virulence | de Jong et al. (2013) | |
| A/chicken/Guangdong/Ts/2004(H9N2), A/chicken/Guangdong/V/2008(H9N2) | BALB/c | E627K | Reduced host antiviral response | Tian et al. (2012) | |
| A/chicken/Shandong/16/05(H9N2) | BALB/c | M147L + E627K | Increased virulence | Wang et al. (2012) | |
| A/Hong Kong/483/97(H5N1) A/Hong Kong/486/97(H5N1) | BALB/c | 627K | Increased virulence | Chen et al. (2007), Hatta et al. (2001) | |
| A/Netherlands/33/03(H7N7) A/Netherlands/219/03(H7N7) | BALB/c | 627K | Increased virulence | Munster et al. (2007) | |
| A/Shanghai/2/2013(H7N9) | BALB/c | E627K | Increased virulence | Mok et al. (2014) | |
| A/Anhui/1/2013(H7N9) | BALB/c | E627K | Increased replication and virulence | Zhang et al. (2014) | |
| Reassortant 1918 H1N1 x avian H1N1 | BALB/c | E627K | Increased mouse virulence | Qi et al. (2012) | |
| A/equine/London/1416/73(H7N7) | BALB/c | E627K | Adaptation and increased neuronal invasion | Shinya et al. (2007) | |
| NP | A/Hong Kong/1/68(H3N2) | CD-1 | D34N, D290N, D480N | Increased mouse virulence Adaptation | Ping et al. (2010) |
| A/Hong Kong/156/97(H5N1) | ddY | E127K | Increased virulence | Hiromoto et al. (2000) | |
| A/Seal/Massachussetts/1/80(H7N7) | BALB/c | N319K | Mouse adaptation | Gabriel et al. (2005, 2008) | |
| NA | r A/Lyon/969/2009(H1N1pdm09) +/− NA from A/Lyon/1337/2007(H1N1) | Balb/cByJ | H275Y | Increased infectivity | Ferraris et al. (2012) |
| A/California/04/09(H1N1pdm09) | Balb/c | H275Y | Increased virulence | Song et al. (2013b) |