title: Persistent infection and suppression of host response by alphaviruses.
abstract: Alphaviruses cause chronic noncytopathic infection in mosquito cells and develop a highly cytopathic infection in a wide variety of cells of vertebrate origin. Upon infection, alphaviruses modify cellular processes to meet the virus needs for propagation. Downregulation of translation and transcription caused by viral infection appears to reduce interferon (IFN) and cytokine gene expression and allows more efficient dissemination of infection. Alphaviruses with mutations in nonstructural protein nsP2 can become less cytopathic and capable of persisting in some vertebrate cell lines for a number of passages. nsP2 likely functions as an important regulator of virus-host cell interactions and plays a significant role in suppressing the antiviral response. Mammalian cells having no defects in type I IFN system react to replication of the nsP2 viral mutants by more efficient activation of IFN and IFN-dependent genes and are capable of eliminating established alphavirus infection. Blocking of IFN-alpha/beta signaling makes mouse fibroblasts unable to stop replication of Sindbis virus (SINV) with mutated nsP2 and leads to persistent infection. Downregulation of transcription and translation during alphavirus infection are quite independent events, and both probably are involved in inhibition of the antiviral response.
authors.affiliation: Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, Texas 77555-1019, USA. ivfrolov@utmb.edu
authors.forename: I
authors.initials: I
authors.lastname: Frolov
mesh_terms: D000524:Alphavirus / Q000235:genetics / Q000502:physiology*; D018354:Alphavirus Infections / Q000235:genetics / Q000276:immunology* / Q000503:physiopathology*; D016207:Cytokines / Q000235:genetics; D005786:Gene Expression Regulation / Q000276:immunology; D016679:Genome, Viral; D006801:Humans; D007372:Interferons / Q000235:genetics; D014176:Protein Biosynthesis; D014779:Virus Replication
chemical_list: D016207:Cytokines; D007372:Interferons