Work

Mechanisms of Protein Kinase PKR-Mediated Amplification of Beta Interferon Induction by C Protein-Deficient Measles Virus

Year: 2009

Type: article

Abstract: The measles virus P gene products V and C antagonize the host interferon (IFN) response, blocking both IFN signaling and production. Using Moraten vaccine strain-derived measles virus and isogenic mutants deficient for either V or C protein production (V(ko) and C(ko), respectively), we observed that the C(ko) virus was a potent inducer of IFN-beta, while induction by V(ko) virus was an order of magnitude lower than that by the C(ko) virus. The parental recombinant Moraten virus did not significantly induce IFN-beta. The enhanced IFN-inducing capacity of the C(ko) virus correlated with an enhanced activation of IFN regulatory factor 3 (IRF-3), NF-kappaB, and ATF-2 in C(ko)-infected compared to V(ko) or parental virus-infected cells. Furthermore, protein kinase PKR and mitochondrial adapter IPS-1 were required for maximal C(ko)-mediated IFN-beta induction, which correlated with the PKR-mediated enhancement of mitogen-activated protein kinase and NF-kappaB activation. Our results reveal multiple consequences of C protein expression and document an important function for PKR as an enhancer of IFN-beta induction during measles virus infection.

Source: Journal of Virology

DOI: 10.1128/jvi.02630-08

Authors: Christopher S. McAllister, Ann M. Toth, Ping Zhang, Patricia Devaux, Roberto Cattaneo, Charles E. Samuel

Institutions: Mayo Clinic, University of California, Santa Barbara

Language: English

Topic: interferon and immune responses

Subfield: Immunology

Field: Immunology and Microbiology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: green

Funders: National Institutes of Health, U.S. Public Health Service, National Institute of Allergy and Infectious Diseases