Table 2. Analysis of molecular features associated with AIV virulence, transmissibility, and antiviral resistance in H5N1 AIV isolated from tigers in Yunnan China, 2014–2015.
| Protein | Molecular feature or amino acid substitution | Phenotypic effect | tig1404 | ig1412 | tig1508 |
|---|---|---|---|---|---|
| HA | Asp94Asn | Increased virus binding to α2-6; enhanced virus fusion | N(Asn) | S(Ser) | N(Asn) |
| Ser133Ala | Increased psuedovirus binding to α2-6 | A(Ala) | A(Ala) | A(Ala) | |
| Ser155Asn | Increased virus binding to α2-6 | D(Asp) | D(Asp) | D(Asp) | |
| Thr156Ala | Increased virus binding to α2-6 and increased transmission in guinea pigs | T(Thr) | A(Ala) | T(Thr) | |
| Asp183Gly | Increased virus binding to α2-6 | N(Asn) | D(Asp) | D(Asp) | |
| Thr188Ile | Increased psuedovirus binding to α2-6 | T(Thr) | I(Ile) | I(Ile) | |
| Lys189Arg | Increased virus binding to α2-6 | N(Asn) | R(Arg) | T(Thr) | |
| Gln192Arg, Gln192His | Increased virus binding to α2-6 | K(Lys) | K(Lys) | Q(Gln) | |
| Lys218Glu | Altered pathogenicity and tissue tropism in mice, emerged in the course of virus replication in a patient | Q(Gln) | R(Arg) | K(Lys) | |
| Gln222Leu | Increased virus binding to α2-6 | Q(Gln) | Q(Gln) | Q(Gln) | |
| Ser223Asn | Increased virus binding to α2-6, emerged in the course of virus replication in a patient (fatal case) | R(Arg) | R(Arg) | S(Ser) | |
| Gly224Ser | Increased virus binding to α2-6 | G(Gly) | G(Gly) | G(Gly) | |
| 323 to 330 (R-X-R/K-R) | Polybasic cleavage motif sequence required for high pathogenicity of H5N1 avian influenza viruses | RERRR*KR | IERRRRKR | RERRR*KR | |
| NA | 49–68 deletion | Enhanced virulence in mice | deletion | deletion | deletion |
| Gln116Leu/Lys/Arg (136 in N2) | Reduced susceptibility to zanamivir and oseltamivir | Q(Gln) | Q(Gln) | H(His) | |
| His254Tyr/Arg (274 in N2) | Reduced susceptibility to oseltamivir and peramivir | Y(Tyr) | Y(Tyr) | Y(Tyr) | |
| PB2 | Glu627Lys | Increased virulence in mice | V(Val) | E(Glu) | E(Glu) |
| Asp701Asn | Mammalian host adaptation Enhanced replication efficiency increased virulence and transmission in guinea pigs | D(Asp) | D(Asp) | N(Asn) | |
| M1 | Asn30Asp | Increased virulence in mice | D(Asp) | D(Asp) | D(Asp) |
| Thr215Ala | Increased virulence in mice | A(Ala) | A(Ala) | A(Ala) | |
| M2 | Val27Ala | Reduced susceptibility to amantadine and rimantadine | V(Val) | V(Val) | G(Gly) |
| Ser31Asn/Gly | Reduced susceptibility to amantadine and rimantadine | S(Ser) | S(Ser) | N(Asn) | |
| NS1 | Pro42Ser | Increased virulence in mice | S (Ser) | S (Ser) | S (Ser) |
| 80–84 deletion | Increased virulence in mice | deletion | deletion | deletion | |
| Asp87Glu | Increased virulence in mice | E(Glu) | E(Glu) | D(Asp) | |
| Leu98Phe | Increased virulence in mice | F(Phe) | F(Phe) | F(Phe) | |
| Ile101Met | Increased virulence in mice | M(Met) | M(Met) | M(Met) | |
| 222–225 (PDZ ligand domain) | Increased virulence in mice | ESEV | ESEV | ESEV |
PB2, basic polymerase 2; PB1, basic polymerase 1; PA, acidic polymerase; HA, hemagglutinin; NP, nucleoprotein; NA, neuraminidase; M, matrix; NS, nonstructural protein.