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. 2021 Aug 26;65(1):1–16. doi: 10.1159/000517057

Table 3.

Amino acid substitutions responsible for increased polymerase activity, viral transmissibility, and virulence of AIVs [24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70]

Function Influenza virus gene segment H5N1a H5N3b H5N3c H5N3d KNU18–91 Reference
Enhanced replication efficiency / virulence PB2 Ms28I M M M M M [24, 25]
A274T A A A A A [24]
R318K R R R R R [26, 27]
R/Q355K R R R R R [26, 28, 29]
Q368R R R R1 R R2 [24, 30, 31]
E391Q E E E E E
H447Q Q Q Q1 Q Q2
K526R K K K K K [24]
M535L M M M M M [32]
I553V I I I I I [24]
Q591K Q Q Q Q Q [33]
E627K E E E E E [34]
D701N D D D D D [35]
S714R S S S S S [36]

PB1 D/A3V V V V1 V V2 [30, 31]
L13P P P P1 P P2 [36]
M/V317I V M M M M [28, 29]
K328N N N N1 N N2 [30, 31]
S678N S S S S S [36]

PB1-F2 N66S N N N N* S2 [23]
87–90 amino acids in length 90 90 90 90 90 [37]

PA S37A A A A1 A A2 [38]
V127I/A V V V V V [27]
S149P S S S S S [24]
L336M L L L L L [27]
A343T S A A A A [39]
K356R K K K K K [40]
I357K T T T T T [24]
S/A515T T T T1 T T2
K615N K K K K K [36]

HA A/I/P/S/T86V A V1 I* V2 [27]
N/D124S D N N N
Q/H/I138L/N Q N1 N N2
N/K189S/R/D/E K K K K [41]
K212E/R/G K E1 E E2 [27]
A263T T A A A
N376T G G G G [42]

NP K470R K K K K K [43]

NA 49–68 deletion Deletion 49–62 No deletion No deletion No deletion No deletion [44]
E119K/D R R R R R [45]
R143K K K K1 K K2 [46]
G147E G G G G G
T223I I I I1 I I2 [28, 29]
H275Y Y Q Q Q Q [47]

NS1 M31I P P P P P [48]
A/P42S S S S1 S* A [27]
G45R G G G G G [49]
D74N D D D D D [50]
Amino acids 80–4 deletion2 Deletion No deletion No deletion No deletion No deletion [51]
D87E S S S S* P [52]
T/D92E E D D D D [27, 29]
L98F M M M M* I [53]
I101M D D D D* E
T/D/V/R/A127N T T N1 N* R [27]
D/G189N D D D D D
S195T/Y S S S S S [27, 48]
S228P S S S S* Q [27]
PDZ domain (X-S/T-X-V at positions 222–225) LARA MART MART MART WRDE [54]

Enhanced binding to α2,6 HA N182K (186 in H3) N N N N [55]
V210I (214 in H3) V V V V [56]
Q222L (226 in H3) Q Q Q Q [57]
S223N (227 in H3) S S S S [58]
G224S (228 in H3) G G G G [57]
N154D, N220K, Q222L, T315I (158, 224, 226, 318 in H3) X, N, Q, T N, N, Q, T N, N, Q, T N, N, Q, T [59]

Reduced susceptibility to NA inhibitors NA V96A (116 in N2) V V V V V [60]
I97V (117 in N2) I T T T T [61]
E99A/G (119 in N2) E E E E E [62]
Q116L (136 in N2) Q Q Q Q Q [63]
V129A (149 in N2) V I I I I [64]
D179G (198 in N2) P N N N N [65]
I203M (222 in N2) N D D D D
S227N (246 in N2) P P P P P [60]
H255Y (274 in N2) Y I I I I [62]
N275S (294 in N2) N N N N N
I97V + I294V (117+314 in N2) I, I T, T T, T T,T T, T [66]
K130N + I203L + S227N (150+222+246 in N2) K, N, P K, N, P K, N, P K, N, P K, N, P [60]

Reduced susceptibility to adamantanes M2 V27A I V V V V [67]
A30S A A A A A [68, 69]
S31N S N S S S [70]

PB, polymerase basic; PA, polymerase acidic; HA, hemagglutinin; NP, nucleoprotein; NA, neuraminidase; M2, matrix 2, NS, nonstructural; AIVs, avian influenza viruses.

a

A/chicken/Nigeria/15VIR339–2/2015 (H5N1) (HPAI).

b

A/goose/Taiwan/01042/2015(H5N3) (HPAI).

c

A/aquatic bird/South Korea/sw007/2015(H5N3).

d

SBD/Korea/KNU SYG06/06 (H5N3) (LPAI).

1

Mutation site of KNU18–91 isolate related to enhanced adaptation in mammals.

2

Mutation site of A/aquatic bird/South Korea/sw007/2015(related to enhanced adaptation in mammals.

*

Different mutation between KNU18–91 and SBD/Korea/KNU SYG06/06 (H5N3).