Open AccessMechanisms of Protein Kinase PKR-Mediated Amplification of Beta Interferon Induction by C Protein-Deficient Measles Virus
Author(s) -
Christopher S. McAllister,
Ann M. Toth,
Ping Zhang,
Patricia Devaux,
Roberto Cattaneo,
Charles E. Samuel
Publication year - 2010
Publication title -
journal of virology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.617
H-Index - 292
eISSN - 1070-6321
pISSN - 0022-538X
DOI - 10.1128/jvi.02630-08
Subject(s) - measles virus , protein kinase r , biology , interferon , virus , eif 2 kinase , virology , protein kinase a , paramyxoviridae , morbillivirus , mononegavirales , sendai virus , microbiology and biotechnology , kinase , mitogen activated protein kinase kinase , cyclin dependent kinase 2 , measles , vaccination , viral disease
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 (Vko and Cko , respectively), we observed that the Cko virus was a potent inducer of IFN-β, while induction by Vko virus was an order of magnitude lower than that by the Cko virus. The parental recombinant Moraten virus did not significantly induce IFN-β. The enhanced IFN-inducing capacity of the Cko virus correlated with an enhanced activation of IFN regulatory factor 3 (IRF-3), NF-κB, and ATF-2 in Cko -infected compared to Vko or parental virus-infected cells. Furthermore, protein kinase PKR and mitochondrial adapter IPS-1 were required for maximal Cko -mediated IFN-β induction, which correlated with the PKR-mediated enhancement of mitogen-activated protein kinase and NF-κB activation. Our results reveal multiple consequences of C protein expression and document an important function for PKR as an enhancer of IFN-β induction during measles virus infection.