| Protein | Amino acid mutation previously reported | Association and function | Amino acid observed in autopsy/culture |
| PB2 | I63T | Decreased pathogenicity in mice | 63I | E627K | Increased replication efficiency in cell culture and enhanced virulence in mice | 627K | Enhanced polymerase activity and mammalian host adaptation | Mammalian host adaptation, increased virulence in mice | Enhanced polymerase activity | H5 virus transmissible among ferrets | M28I, A274T, K526R, I553V, L607V | Decreased polymerase activity | 28M, 274A,526K, 553I, 607L | L89V, G309D, T339K, R477G, I495V, A676T | Enhanced polymerase activity, increased virulence in mice | 89V, 309D, 339K, 477G, 495V, 676T | PB1 | K207R | Decreased polymerase activity in mammalian cells | 207K | Y436H | Decreased polymerase activity and virulence in mallards, ferrets, and mice | 436Y | T677M | Decreased virulence in mice | 677T | V3A, N328K, N375S | Decreased replication efficiency and virulence in ferrets | 3V, 328N, 375N | V473L, P598L | Decreased polymerase activity and replication efficiency | 473V, 598L | PA | P149S, R266H, K357I, T515S | Decreased polymerase activity in mammalian cells | 149S, 266R, 357I, 515T | NA | 49-68 deletion | Enhanced virulence in mice | 49-68 deletion | M1 | N30D, T139A, T215A | Increased virulence in mice | 30D, 139T, 215A | M2 | L26F, V27A, G34E, A30V/T/S, S31N/G | Reduced susceptibility to amantadine and rimantadine | 26I, 27V, 34G, 30A, 31 N | NS1 | 80-84 deletion, P42S, D87E, L98F, L101M | Increased virulence in mice | 80-84 deletion,42S, 87D, 98F, 101M | ESEV (in PDZ domain) | Increased virulence in mice | ESEV(in PDZ domain) |
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