Induction of GADD34 Is Necessary for dsRNA-Dependent Interferon-β Production and Participates in the Control of Chikungunya Virus Infection

• DOI: 10.1371/journal.ppat.1002708
• Publication Date: 2012-05-17T21:02:42Z
• Authors: Giovanna Clavarino; Nuno Cláudio; Thérèse Couderc; Alexandre Dalet; Delphine Judith; Voahirana Camosseto; Enrico K. Schmidt; Till Wenger; Marc Lecuit; Evelina Gatti; Philippe Pierre
• Keywords: Protein kinase R; IRF3; EIF-2 kinase; RNA Silencing

Nucleic acid sensing by cells is a key feature of antiviral responses, which generally result in type-I Interferon production and tissue protection. However, detection double-stranded RNAs virus-infected promotes two concomitant apparently conflicting events. The dsRNA-dependent protein kinase (PKR) phosphorylates translation initiation factor 2-alpha (eIF2α) inhibits synthesis, whereas cytosolic DExD/H box RNA helicases induce expression type I-IFN other cytokines. We demonstrate that the phosphatase-1 cofactor, growth arrest DNA damage-inducible 34 (GADD34/Ppp1r15a), an important component unfolded response (UPR), absolutely required for IL-6 mouse embryonic fibroblasts (MEFs) to dsRNA. GADD34 MEFs dependent on PKR activation, linking microbial with ATF4 branch UPR. importance this link anti-viral immunity underlined extreme susceptibility GADD34-deficient neonate mice Chikungunya virus infection.