Regulation of coronavirus-induced host responses

Abstract

Coronaviruses (CoV) are positive-stranded RNA viruses with a genome of approximately 30 kb. Most human coronaviruses cause upper respiratory tract infections. Here we applied microarray analysis to assess global changes in cellular expression profiles during acute cytopathic coronavirus infection. We demonstrated that MHV infection in fibroblast-like cells triggers very few changes in cellular mRNA levels in the first hours of infection and that infection of fibroblasts with MHV and SARS-CoV does not result in a significant induction of IFN production through intracellular detection by RNA helicases. Data from additional experiments suggest that the absence of IRF-3 activation is a general characteristic of group 2 coronaviruses. Furthermore we show that MHV and SARS-CoV do not actively block IRF-3 activation via either RIG-I or MDA-5 as they are unable to inhibit IRF-3 translocation upon Sendai virus infection or poly (I:C) transfection, respectively. Finally, we show that SARS-CoV and MHV induce ER stress and chemokine mRNA transcription during infection in vitro. Expression of the viral spike protein significantly induced ER stress and Cxcl2 mRNA upregulation. However, translation of these cellular mRNAs is severely reduced, resulting in no significant CXCL2 and HERPUD1 protein synthesis in infected cells despite their increased mRNA concentrations.