Chikungunya virus induces IPS-1-dependent innate immune activation and protein kinase R-independent translational shutoff
Autor(es): White Laura K, Sali Tina, Alvarado David, Gatti Evelina, Pierre Philippe, Streblow Daniel, Defilippis Victor R
Resumo: Chikungunya virus (CHIKV) is an arthritogenic mosquito-transmitted alphavirus that is undergoing reemergence in areas around the Indian Ocean. Despite the current - potential danger posed by this virus, we know surprisingly little about the induction - evasion of CHIKV-associated antiviral immune responses. With this in mind we investigated innate immune reactions to CHIKV in human fibroblasts, a demonstrable in vivo target of virus replication - spread. We show that CHIKV infection leads to activation of the transcription factor interferon regulatory factor 3 (IRF3) - subsequent transcription of IRF3-dependent antiviral genes, including beta interferon (IFN-?). IRF3 activation occurs by way of a virus-induced innate immune signaling pathway that includes the adaptor molecule interferon promoter stimulator 1 (IPS-1). Despite strong transcriptional upregulation of these genes, however, translation of the corresponding proteins is not observed. We further demonstrate that translation of cellular (but not viral) genes is blocked during infection - that although CHIKV is found to trigger inactivation of the translational molecule eukaryotic initiation factor subunit 2? by way of the double-str-ed RNA sensor protein kinase R, this response is not required for the block to protein synthesis. Furthermore, overall diminution of cellular RNA synthesis is also observed in the presence of CHIKV - transcription of IRF3-dependent antiviral genes appears specifically blocked late in infection. We hypothesize that the observed absence of IFN-? - antiviral proteins during infection results from an evasion mechanism exhibited by CHIKV that is dependent on widespread shutoff of cellular protein synthesis - a targeted block to late synthesis of antiviral mRNA transcripts.
Imprenta: Journal of Virology, v. 85, n. 1, p. 606-620, 2011
Identificador do objeto digital: 10.1128/JVI.00767-10
Descritores: Chikungunya virus - Biosynthesis ; Chikungunya virus - Cell ; Chikungunya virus - Immune response ; Chikungunya virus - Pathogenesis ; Chikungunya virus - Protein synthesis ; Chikungunya virus - Proteins ; Chikungunya virus - RNA ; Chikungunya virus - Cytokines ; Chikungunya virus - Immune response ; Chikungunya Virus - Virus ; Chikungunya virus - Vaccine ; Chikungunya virus - Immunology
Data de publicação: 2011
