Suppression of interferon response gene expression in cells persistently infected with mumps virus, and restoration from its suppression by treatment with ribavirin.
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.
Fujii
N
N
Department of Microbiology, School of Medicine, Sapporo Medical University, South 1, West 17, Chuou-Ku, Sapporo, Japan.
Yokosawa
N
N
Shirakawa
S
S
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
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