TABLE 4.
Viral mechanisms of PKR inhibition
| Target | Virus/inhibitor | Mechanism of action | Reference(s) |
|---|---|---|---|
| dsRBMs | Adenovirus/VAI RNA | Competitively inhibits dsRNA-binding reaction | 320, 321 |
| Epstein-Barr virus/EBER RNAs | Competitively inhibits dsRNA-binding reaction | 64, 70 | |
| Vaccinia virus/E3L | Sequesters dsRNA | 55, 475 | |
| Influenza virus/NS1 | Sequesters dsRNA | 312 | |
| Reovirus/ς3 | Sequesters dsRNA | 20, 307, 493 | |
| HIV TAR RNA | Competitively inhibits activator dsRNA binding; may activate PKR; could target TAR RNA binding protein to PKR | 169, 314 | |
| TAR RNA binding protein | Binds to PKR, inhibits kinase activity; may sequester dsRNA | 24, 73 | |
| Dimerization | Influenza virus/P58IPK | Disrupts dimerization | 294 |
| Hepatitis C virus/NS5A | Disrupts dimerization | 129, 133, 134 | |
| Substrate interaction | Vaccinia virus/K3L | Binds to PKR as a pseudosubstrate; blocks PKR-substrate interaction | 21, 255 |
| HIV Tat | 39, 327 | ||
| Expression and stability | Poliovirus | Induces PKR proteolysis | 29, 30 |
| HIV Tat | Lowers expression of PKR | 397 | |
| Regulation of eIF2α | HSV/γ134.5 gene product | Complexes with eIF2α and induces an eIF2α phosphatase | 188, 338 |
| Simian virus 40/T antigen | Targets processes downstream of eIF2α | 386, 444 |