Induction of GADD34 is necessary for dsRNA-dependent interferon-? production and participates in the control of Chikungunya virus infection
Autor(es): Clavarino Giovanna, Cláudio Nuno, Couderc Thérèse, Dalet Alexandre, Judith Delphine, Camosseto Voahirana, Schmidt Enrico K, Wenger Till, Lecuit Marc, Gatti Evelina, Pierre Philippe
Resumo: Nucleic acid sensing by cells is a key feature of antiviral responses, which generally result in type-I Interferon production - tissue protection. However, detection of double-str-ed RNAs in virus-infected cells promotes two concomitant - apparently conflicting events. The dsRNA-dependent protein kinase (PKR) phosphorylates translation initiation factor 2-alpha (eIF2?) - inhibits protein synthesis, whereas cytosolic DExD/H box RNA helicases induce expression of type I-IFN - other cytokines. We demonstrate that the phosphatase-1 cofactor, growth arrest - DNA damage-inducible protein 34 (GADD34/Ppp1r15a), an important component of the unfolded protein response (UPR), is absolutely required for type I-IFN - IL-6 production by mouse embryonic fibroblasts (MEFs) in response to dsRNA. GADD34 expression in MEFs is dependent on PKR activation, linking cytosolic microbial sensing with the ATF4 branch of the UPR. The importance of this link for anti-viral immunity is underlined by the extreme susceptibility of GADD34-deficient fibroblasts - neonate mice to Chikungunya virus infection.
Imprenta: PLoS Pathogens, v. 8, n. 5, p. e1002708, 2012
Identificador do objeto digital: 10.1371/journal.ppat.1002708
Descritores: Chikungunya virus - Biosynthesis ; Chikungunya virus - Cell ; Chikungunya virus - DNA ; Chikungunya virus - Molecular structure ; Chikungunya virus - Pathogenesis ; Chikungunya virus - Protein synthesis ; Chikungunya virus - Proteins ; Chikungunya virus - RNA ; Chikungunya virus - Cytokines ; Chikungunya virus - Viral infections ; Chikungunya Virus - Virus ; Chikungunya virus - Chikungunya fever ; Chikungunya virus - Immunology
Data de publicação: 2012
