The effect of the vaccinia K1 protein on the PKR-eIF2α pathway in RK13 and HeLa cells |
| |
Authors: | Kristen L Willis Samir Patel Yan Xiang Joanna L Shisler |
| |
Institution: | aDepartment of Microbiology, College of Medicine, University of Illinois at Urbana-Champaign, 601 S. Goodwin Avenue, Urbana, IL 61801, USA;bDepartment of Microbiology and Immunology, University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, San Antonio, TX 78229, USA |
| |
Abstract: | Activated PKR protein regulates downstream anti-viral effects, including inhibition of translation. Thus, many viruses encode proteins to inhibit PKR. Here, we provide evidence that the vaccinia virus K1 protein, a host-range protein, possesses this function. First, the expression of the wild-type K1 protein was necessary to inhibit virus-induced eIF2α phosphorylation, an indirect measure of PKR activation, in RK13 and HeLa cells. Second, virus-induced eIF2α phosphorylation no longer occurred in PKR-deficient HeLa cells, suggesting PKR was responsible for vaccinia virus-induced eIF2α modification. Third, in normal HeLa cells, K1 protein expression also prevented virus-mediated PKR phosphorylation (activation). Residues in the C-terminal portion of the ANK2 region of K1 were identified as necessary for this inhibitory phenotype. Interestingly, mutant viruses that failed to inhibit PKR activation, such as S2C#2, also did not replicate in HeLa cells, suggesting that K1's inhibition of PKR was required for a productive infection. In support of this theory, when PKR was absent from HeLa cells, there was a modest restoration of viral protein synthesis during S2C#2 infection. However, the increased protein synthesis was insufficient for a productive infection. |
| |
Keywords: | Vaccinia PKR eIF2α K1L Host range |
本文献已被 ScienceDirect 等数据库收录! |
|