Table 2.
Key genetic mutations in mild, severe and fatal cases of confirmed infection with avian H7N9 virus from March 31 of 2013 to December 31 of 2014
| Segment | Mutation | Vaccine candidate isolate | Human isolates | p1 value | Non-human isolates | p2 value | |||
|---|---|---|---|---|---|---|---|---|---|
| A/Anhui/1/2013/H7N9 | Mild (N = 14) | Severe (N = 50) | Fetal (N = 35) | Chicken (N = 43) | Environmental (N = 30) | ||||
| HA | RBS positions (H3 numbering) | ||||||||
| Q226L | L | 8/10 (80.0 %) | 49/50 (98.0 %) | 31/34 (91.2 %) | 0.080 | 37/43 (86.0 %) | 19/30 (63.3 %) | <0.001 | |
| Q226I | 0/10 (0.0 %) | 0/50 (0.0 %) | 2/34 (5.9 %) | 0.165 | 0/43 (0.0 %) | 0/30 (0.0 %) | – | ||
| Q226P | 0/10 (0.0 %) | 1/50 (2.0 %) | 0/34 (0.0 %) | 0.641 | 0/43 (0.0 %) | 0/25 (0.0 %) | – | ||
| G228S | G | 0/10 (0.0 %) | 0/50 (0.0 %) | 0/34 (0.0 %) | – | 0/43 (0.0 %) | 0/30 (0.0 %) | – | |
| Antigenic site (H3 numbering) | |||||||||
| R57K (antigenic site E) | R | 6/10 (60.0 %) | 15/50 (30.0 %) | 6/34 (17.6 %) | 0.234 | 4/43 (9.30 %) | 5/30 (16.7 %) | 0.052 | |
| R57M (antigenic site E) | 0/10 (0.0 %) | 4/50 (8.0 %) | 0/34 (0.0 %) | 5/43 (11.6 %) | 1/30 (3.3 %) | ||||
| T133A (antigenic site A) | T | 1/10 (10.0 %) | 5/50 (10.0 %) | 3/34 (8.8 %) | 0.263 | 0/43 (0.0 %) | 1/30 (3.3 %) | 0.09 | |
| G186V (antigenic site B) | V | 9/10 (90.0 %) | 49/50 (98.0 %) | 33/34 (97.1 %) | 0.419 | 43/43 (100.0 %) | 30/30 (100.0 %) | 0.247 | |
| N276D (antigenic site C) | N | 3/10 (30.0 %) | 6/50 (12.0 %) | 1/34 (2.9 %) | 0.046 | 0/43 (0.0 %) | 0/30 (0.0 %) | <0.001 | |
| No report (H3 numbering) | |||||||||
| E114K | E | 2/10 (20.0 %) | 4/50 (8.0 %) | 1/34 (2.9 %) | 0.191 | 1/43 (2.3 %) | 0/30 (0.0 %) | 0.073 | |
| L168I | L | 2/10 (20.0 %) | 7/50 (14.0 %) | 0/34 (0.0 %) | 0.050 | 0/43 (0.0 %) | 0/30 (0.0 %) | 0.001 | |
| NA | Related to drug resistance | ||||||||
| E120V | E | 0/10 (0.0 %) | 0/48 (0.0 %) | 0/33 (0.0 %) | – | 0/43 (0.0 %) | 0/30 (0.0 %) | – | |
| V248I | V | 1/10 (10.0 %) | 4/48 (8.3 %) | 3/33 (9.1 %) | 0.983 | 1/43 (2.3 %) | 1/30 (3.3 %) | 0.614 | |
| V251I | I | 10/10 (100.0 %) | 47/48 (97.9 %) | 32/33 (97.0 %) | 0.846 | 43/43 (100.0 %) | 30/30 (100.0 %) | 0.695 | |
| H276Y | H | 0/10 (0.0 %) | 0/48 (0.0 %) | 0/33 (0.0 %) | – | 0/43 (0.0 %) | 0/30 (0.0 %) | – | |
| R294K | R | 0/10 (0.0 %) | 1/48 (2.1 %) | 4/33 (12.1 %) | 0.01 | 0/43 (0.0 %) | 0/30 (0.0 %) | 0.01 | |
| N296S | N | 0/10 (0.0 %) | 0/48 (0.0 %) | 0/33 (0.0 %) | – | 0/43 (0.0 %) | 0/30 (0.0 %) | – | |
| N337T | N | 1/10 (10.0 %) | 7/41 (17.1 %) | 3/33 (9.1 %) | 0.571 | 1/43 (2.3 %) | 1/30 (3.3 %) | 0.125 | |
| PB1 | Increased H5 virus transmission among ferrets | ||||||||
| I368V | V | 11/11 (100.0 %) | 39/41 (95.1 %) | 27/31 (87.1 %) | 0.261 | 35/35 (100.0 %) | 30/30 (100.0 %) | 0.045 | |
| Increased replication in mammalian cells | |||||||||
| L598P/M | L | 0/11 (0.0 %) | 0/41 (0.0 %) | 1/31 (3.2 %) | 0.428 | 0/35 (0.0 %) | 0/30 (0.0 %) | 0.434 | |
| PB1-F2 | Increased pathogenicity in mice | ||||||||
| 25AA | 90AA | 1/11 (9.1 %) | 6/41 (14.6 %) | 1/31 (3.2 %) | 0.267 | 9/35 (25.7 %) | 11/30 (36.7 %) | 0.03 | |
| 57AA | 2/11 (18.2 %) | 2/41 (4.9 %) | 0/31 (0.0 %) | 0.054 | 0/35 (0.0 %) | 0/30 (0.0 %) | 0.200 | ||
| 76AA | 0/11 (0.0 %) | 0/41 (0.0 %) | 2/31 (6.5 %) | 0.179 | 2/35 (5.7 %) | 0/30 (0.0 %) | 0.356 | ||
| 90AA | 90AA | 8/11 (72.7 %) | 33/41 (80.5 %) | 28/31 (90.3 %) | 0.333 | 24/35 (68.6 %) | 19/30 (63.3 %) | 0.05 | |
| PB2 | Enhanced polymerase activity and increased virulence in mice | ||||||||
| L89V | L | 9/9 (100.0 %) | 44/44 (100.0 %) | 30/30 (100.0 %) | – | 43/43 (100.0 %) | 30/30 (100.0 %) | – | |
| K191E | K | 6/9 (66.7 %) | 16/44 (36.4 %) | 9/30 (30.0 %) | 0.119 | 7/43 (16.3 %) | 6/30 (20.0 %) | 0.016 | |
| N559T | N | 6/9 (66.7 %) | 18/44 (40.9 %) | 7/30 (23.3 %) | 0.048 | 7/43 (16.3 %) | 8/30 (26.7 %) | 0.011 | |
| M570I | M | 5/9 (55.6 %) | 13/44 (29.5 %) | 7/30 (23.3 %) | 0.80 | 4/43 (9.3 %) | 7/30 (23.3 %) | 0.026 | |
| Q591K/L | Q | 1/9 (11.1 %) | 1/44 (2.3 %) | 1/30 (3.3 %) | 0.430 | 0/43 (0.0 %) | 0/30 (0.0 %) | 0.214 | |
| E627K | K | 3/9 (33.3 %) | 30/44 (68.2 %) | 26/30 (86.7 %) | 0.006 | 8/43 (18.6 %) | 0/30 (0.0 %) | <0.001 | |
| D701N | D | 1/9 (11.1 %) | 4/44 (9.1 %) | 2/30 (6.7 %) | 0.860 | 0/43 (0.0 %) | 0/30 (0.0 %) | 0.119 | |
| PA | Species-associated signature positions | ||||||||
| V100A | A | 4/8 (50.0 %) | 30/41 (73.2 %) | 27/30 (90.0 %) | 0.038 | 28/35 (80.0 %) | 24/30 (80.0 %) | 0.137 | |
| I308V | I | 0/8 (0.0 %) | 3/41 (7.3 %) | 0/30 (0.0 %) | 0.236 | 0/35 (0.0 %) | 1/30 (3.3 %) | 0.250 | |
| K356R | R | 6/8 (75.0 %) | 34/41 (82.9 %) | 28/30 (93.3 %) | 0.289 | 34/35 (97.1 %) | 30/30 (100.0 %) | 0.024 | |
| S409N | N | 7/8 (87.5 %) | 39/41 (95.1 %) | 29/30 (96.7 %) | 0.574 | 31/35 (88.6 %) | 25/28 (89.3 %) | 0.635 | |
| T618K | T | 0/8 (0.0 %) | 0/41 (0.0 %) | 1/30 (3.3 %) | 0.437 | 0/35 (0.0 %) | 0/30 (0.0 %) | 0.430 | |
| NP | Increased virulence in mice | ||||||||
| N321S | N | 0/11 (0.0 %) | 1/41 (2.4 %) | 1/32 (3.1 %) | 0.842 | 1/34 (2.9 %) | 1/30 (3.3 %) | 0.983 | |
| D375E | D | 4/11 (36.4 %) | 7/41 (17.1 %) | 4/32 (12.5 %) | 0.200 | 1/34 (2.9 %) | 4/30 (13.3 %) | 0.071 | |
| NS1 | Increased virulence in mice | ||||||||
| P42S | S | 11/11 (100.0 %) | 42/42 (100.0 %) | 32/32 (100.0 %) | – | 36/36 (100.0 %) | 30/30 (100.0 %) | – | |
| T92A | T | 1/11 (9.1 %) | 0/42 (0.0 %) | 1/32 (3.1 %) | 0.195 | 0/36 (0.0 %) | 0/30 (0.0 %) | 0.119 | |
| PDZ binding motif | Deletion | Deletion | Deletion | Deletion | – | Avian type | Avian type | – | |
| M1 | Increased virulence in mice | ||||||||
| N30D | D | 9/9 (100.0 %) | 44/44 (100.0 %) | 31/31 (100.0 %) | – | 36/36 (100.0 %) | 30/30 (100.0 %) | – | |
| T215A | A | 9/9 (100.0 %) | 44/44 (100.0 %) | 31/31 (100.0 %) | – | 36/36 (100.0 %) | 30/30 (100.0 %) | – | |
| M2 | Antiviral resistance (amantadine) | ||||||||
| S31N | N | 9/9 (100.0 %) | 44/44 (100.0 %) | 31/31 (100.0 %) | – | 36/36 (100.0 %) | 30/30 (100.0 %) | – | |
Single letters refer to the amino acid (aa) found in the indicated protein at a specific site. The numbering starts with the first methionine codon for these proteins
p1 value: comparison of the mutation frequency among the isolates from mild, severe and fatal cases
p2 value: comparison of the mutation frequency between human and non-human isolates
Qualitative measurements are presented as relative and absolute frequencies. Chi-square (χ2) tests were applied to compare the distribution of the different variables of qualitative measurements. Fisher’s exact test was used in the analysis of contingency tables when the sample sizes were small
“-” denotes no difference between the groups