title: Suppression of interferon response gene expression in cells persistently infected with mumps virus, and restoration from its suppression by treatment with ribavirin.
abstract: Persistent infections with mumps virus were established in human B-lymphoid cell line Akata and in the human chronic myelogenous leukaemia cell line K562. Even after IFN treatment a drastic decrease in STAT-1alpha (signal transducers and activators of transcription-1alpha), STAT-2 and p48 (ISGF-3gamma: IFN-stimulated gene factor-3gamma), which are closely correlated with the IFN-signaling pathway, was found in these persistently infected cells (Akata-MP1 and K-MTP). Therefore, the IFN-signaling pathway is thought to be defective in these persistently infected cells. In other words, most of the IFN-inducible genes in these cells persistently infected with mumps virus may not be able to respond to IFN treatment. Indeed, poor induction of 2',5'-oligoadenylate synthetase (2-5AS), dsRNA activated protein kinase (PKR), and MxA protein mRNAs were demonstrated in these cell lines after IFN treatment. Expression of MHC class-I antigen was also significantly reduced in the persistently infected cell lines as compared with that of uninfected control cells. HLA antigen was augmented by IFN-alpha in Akata and K562 cells, but not in persistently infected cells. Furthermore, suppression of IFN-induced 2-5AS induction and MHC class-I expression was restored by treatment of persistently infected cells with ribavirin through inhibition of virus replication. The result of restoration was also confirmed by IFN-induced STAT-1 induction in persistently infected cells treated with ribavirin.
authors.affiliation: Department of Microbiology, School of Medicine, Sapporo Medical University, South 1, West 17, Chuou-Ku, Sapporo, Japan.
authors.forename: N
authors.initials: N
authors.lastname: Fujii
authors.forename: N
authors.initials: N
authors.lastname: Yokosawa
authors.forename: S
authors.initials: S
authors.lastname: Shirakawa
mesh_terms: D000998:Antiviral Agents / Q000494:pharmacology; D001402:B-Lymphocytes / Q000187:drug effects / Q000821:virology; D004268:DNA-Binding Proteins; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D050832:Interferon-Stimulated Gene Factor 3; D007372:Interferons / Q000502:physiology*; D020014:K562 Cells; D009109:Mumps virus / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism*; D012254:Ribavirin / Q000494:pharmacology*; D015398:Signal Transduction; D014157:Transcription Factors / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism
chemical_list: D000998:Antiviral Agents; D004268:DNA-Binding Proteins; D050832:Interferon-Stimulated Gene Factor 3; D014157:Transcription Factors; C079868:gamma interferon activation factor; D012254:Ribavirin; D007372:Interferons