TABLE 3.
Molecular markers identified in H5 viruses in Vietnam
| Gene | Mutation location/phenotypic consequence (s) | Mutation | Molecular marker (% of viruses with substitution) or amino acids |
|||
|---|---|---|---|---|---|---|
| Clade 1 | Clade 2.3.2.1c | Clade 2.3.4.4 (H5N6) | Clade 7.2 | |||
| HA | Antigenic site C | D43A | A (4.8) | |||
| Antigenic site E | K48R | R (95.2) | ||||
| Antigenic site E | S84G | G (100) | ||||
| Antigenic site B; increased α2-6 binding | S123P | P (90.5) | S (85.7) | P (30.7) | ||
| Antigenic site A | E126N | N (100) | ||||
| Antigenic site A; increased α2-6 binding | S133A | A (100) | (100) | |||
| Antigenic site A | Q138L | L (19.0) | ||||
| Antigenic site A | G138E | E (100) | ||||
| Antigenic site A | K140N/Q | Q (90.5); N (4.8) | ||||
| Antigenic site A | S141P | P (3.9) | P (7.7) | |||
| Antigenic site B; receptor binding | L151I | I (87.0) | T (31.0) | |||
| Antigenic site B | D154N/G | N (10.4); G (2.6) | ||||
| Antigenic site B | S155N | N (47.6) | ||||
| Antigenic site B; predicted loss of glycosylation; increased α2-6 binding; increased transmission in mammalian models | T156A | A (100) | ||||
| Antigenic site B | S181P | P (23.08) | ||||
| Antigenic site B | T182A | A (100) | ||||
| Antigenic site B | D183N | N (61.53) | ||||
| Antigenic site B | A184E | E (23.08) | ||||
| Antigenic site B | V184K | K (100) | ||||
| Antigenic site B | K187M | M (100) | ||||
| Antigenic site B | P188S | S (100) | ||||
| Antigenic site B; increased virus binding to α2-6 | R189K | K (3.9) | ||||
| Antigenic site B | Q192K | K (100) | ||||
| Antigenic site B | P193S | S (100) | ||||
| Antigenic site B | T195N | N (9.5) | ||||
| Antigenic site D | V210T | T (100) | ||||
| Edge of the receptor binding site | R212K | K (87.0) | ||||
| Increased virus binding to α2-6; antigenic site D | S223R | R (6.5) | R (100) | |||
| Antigenic site D | M225I | I (100) | ||||
| Antigenic site C | N273D | D (4.8) | ||||
| Antigenic site C | S275N | N (79.2) | ||||
| Highly pathogenic cleavage peptides | PQRE/KE/GRRKKR↓G | PQR/KERRRKR↓G | PLREKRRKR↓G | PQIEGRRRKRG↓G | ||
| NA | Stalk deletion | 59–69del | del (30.8) | |||
| Reduced susceptibility to zanamivir | V129A | A (80.9) | ||||
| Reduced susceptibility to oseltamivir | I203V | A (4.8) | ||||
| Associated with reduced inhibition by NAIs | R430Q | Q (4.8) | ||||
| PB2 | Enhanced polymerase activity; increased virulence in mice | T339K | K (42.1) | K (94.4) | K (61.5) | K (100) |
| Reduction in replication efficacy in cell culture and virulence in mice and ferrets | R368Q | Q (42.1) | Q (97.2) | Q (68.2) | ||
| Reduction in replication efficiency in cell culture and virulence in mice and ferrets | Q391E | E (100) | E (100) | E (100) | E (100) | |
| Increased replication efficiency in cell culture and enhanced virulence in mice; mammalian host adaptation | K627E | E (100) | E (100) | E (100) | E (100) | |
| PB1 | Decreased replication efficiency and virulence in ferrets | N328K | K (1.41) | |||
| Decreased replication efficiency and virulence in ferrets | N375S | S (10.5) | ||||
| PB1-F2a | Increased pathogenicity in mice | |||||
| PA | K356R | R (1.0) | ||||
| M2 | Reduced susceptibility to amantadine/rimantadine | V27A | A (7.69) | |||
| Reduced susceptibility to amantadine/rimantadine | A30S | S (1.41) | ||||
| Reduced susceptibility to amantadine/rimantadine | N31S | S (42.1) | S (100) | S (100) | ||
| NS1b | Altered virulence in mice | D92E | E (100) | E (100) | E (100) | |
| Altered virulence in mice, PDZ motif | 227–230 | |||||
| NS2 | Decreased antiviral response in host | T47A | A (100) | A (100) | A (100) | |
| Decreased antiviral response in host | M51I | I (100) | ||||
a
Protein lengths for clade 1, 90 amino acids (aa) (80% density) and 57 aa (20% density); protein length for clade 2.3.2.1c, 57 aa (100% density); protein length for clade 2.3.4.4 (H5N6), 57 aa (100% density); protein length for clade 7.2, 90 aa (100% density).
b
NS1 also showed a deletion of amino acids 80 to 84 that was associated with altered virulence in mice for all four clades.