Protein Kinase PKR Mediates the Apoptosis Induction and Growth Restriction Phenotypes of C Protein-Deficient Measles Virus
Year: 2008
Type: article
Abstract: The measles virus (MV) accessory proteins V and C play important roles in MV replication and pathogenesis. Infection with recombinant MV lacking either V or C causes more cell death than infection with the parental vaccine-equivalent virus (MVvac), and C-deficient virus grows poorly relative to the parental virus. Here, we show that a major effector of the C phenotype is the RNA-dependent protein kinase PKR. Using human HeLa cells stably deficient in PKR as a result of RNA interference-mediated knockdown (PKR(kd) cells), we demonstrated that a reduction in PKR partially rescued the growth defect of C knockout (C(ko)) virus but had no effect on the growth of either wild-type (WT) or V knockout (V(ko)) virus. Increased growth of the C(ko) virus in PKR(kd) cells correlated with increased viral protein expression, while defective growth and decreased protein expression in PKR-sufficient cells correlated with increased phosphorylation of PKR and the alpha subunit of eukaryotic initiation factor 2. Furthermore, infection with WT, V(ko), or especially C(ko) virus caused significantly less apoptosis in PKR(kd) cells than in PKR-sufficient cells. Although apoptosis induced by C(ko) virus infection in PKR-sufficient cells was blocked by a caspase antagonist, the growth of C(ko) virus was not restored to the WT level by treatment with this pharmacologic inhibitor. Taken together, these results indicate that PKR plays an important antiviral role during MV infection but that the virus growth restriction by PKR is not dependent upon the induction of apoptosis. Furthermore, the results establish that a principal function of the MV C protein is to antagonize the proapoptotic and antiviral activities of PKR.
Source: Journal of Virology
DOI: 10.1128/jvi.01669-08
Institutions: University of California, Santa Barbara, Mayo Clinic
Language: English
Topic: Virology and Viral Diseases
Subfield: Epidemiology
Field: Medicine
Domain: Health Sciences
Open Access status: green
Awards: Immunosuppression and Innate Immunity Control by Morbilliviruses, G1364809570, G1837174880, Mechanism of Interferon Action, G6016607408, Control of innate immunity and apoptosis by Measles virus P, V and C proteins, MECHANISM OF INTERFERON ACTION, Interferon Action and Protein Phosphorylation
OpenAlex ID: W2120775721