Table 3.
Polymorphisms/mutations observed in the HSV-1 TK.
HSV Type | Serial number | Polymorphism/Mutation | Found in sample | Domain | Previously reported mutation | Function | Sensitivity/resistance to ACV | References |
---|---|---|---|---|---|---|---|---|
HSV-1 isolates | 1 | G21V | PB3PP, HM3PP | Non-conserved | Not reported | ACV sensitive | Not applicable (NA) | This study |
2 | G56V | RBG-V2 | ATP-binding site | G56S | ACV resistant | IC50 1.9 µM: 11-fold | 16 | |
3 | G56A | MAQ-V1, MAQ-A1 | ATP-binding site | G56S | ACV resistant | IC50 1.9 µM: 11-fold | 16 | |
4 | Q89R | RBG-V2 | Non-conserved | Q89R | Natural polymorphism | NA | 17 | |
5 | A147G | AB2-A2, AB2-V1 | Non-conserved | Not reported | Unknown | Not done | 18 | |
6 | D162N | AB2-A2, AB2-V1 | Conserved region (nt binding site) | D162N | ACV resistant | IC50 11.0 µM: 64-fold | 19,20 | |
7 | V191G | AB2-A2, AB2-V1 | Non-conserved | V191A | Spontaneous mutation | NA | 18 | |
8 | R212K | AB2-A2, AB2-V1 | Non-conserved | Not reported | ACV resistant | 70% resistance to ACV at 4.4 µM (> IC90) | This study | |
9 | E225K | AM-V2, WTB-V2, WTB-A2, AB2-A2, AB2-V1 | Non-conserved | Not reported | ACV resistant | 60% resistance to ACV at 4.4 µM (> IC90) | This study | |
10 | S263L | WTB-V2, WTB-A2 | Non-conserved | S263L | Natural Polymorphism | NA | 21 | |
11 | P300Del | MAQ-V1, MAQ-A1 | Non-conserved | Not reported | ACV resistant | Fully-resistant, IC50 > 44 µM | This study | |
HSV-2 isolates | 12 | G39E | AKS-A1, BKN-A1 | Non-conserved | G39E | Natural polymorphism | NA | 22 |
13 | N78D | AKS-A1 | Non-conserved | N78D | Natural polymorphism | NA | 23 | |
14 | L263P | AKS-A1 | Non-conserved | Not reported | Spontaneous mutation | NA | This study |