RRC ID 54089
Author Odkhuu E, Komatsu T, Koide N, Naiki Y, Takeuchi K, Tanaka Y, Tsolmongyn B, Jambalganiin U, Morita N, Yoshida T, Gotoh B, Yokochi T.
Title Sendai virus C protein limits NO production in infected RAW264.7 macrophages.
Journal Innate Immun
Abstract To suppress virus multiplication, infected macrophages produce NO. However, it remains unclear how infecting viruses then overcome NO challenge. In the present study, we report the effects of accessory protein C from Sendai virus (SeV), a prototypical paramyxovirus, on NO output. We found that in RAW264.7 murine macrophages, a mutant SeV without C protein (4C(-)) significantly enhanced inducible NO synthase (iNOS) expression and subsequent NO production compared to wild type SeV (wtSeV). SeV 4C(-) infection caused marked production of IFN-β, which is involved in induction of iNOS expression via the JAK-STAT pathway. Addition of anti-IFN-β Ab, however, resulted in only marginal suppression of NO production. In contrast, NF-κB, a primarily important factor for transcription of the iNOS gene, was also activated by 4C(-) infection but not wtSeV infection. Induction of NO production and iNOS expression by 4C(-) was significantly suppressed in cells constitutively expressing influenza virus NS1 protein that can sequester double-stranded (ds)RNA, which triggers activation of signaling pathways leading to activation of NF-κB and IRF3. Therefore, C protein appears to suppress NF-κB activation to inhibit iNOS expression and subsequent NO production, possibly by limiting dsRNA generation in the context of viral infection.
Volume 24(7)
Pages 430-438
Published 2018-10
DOI 10.1177/1753425918796619
PMID 30189760
MeSH Animals Gene Expression Regulation Interferon Regulatory Factor-3 / metabolism Janus Kinases / metabolism Macrophages / physiology* Mice Mutation / genetics NF-kappa B / metabolism Nitric Oxide / metabolism Nitric Oxide Synthase Type II / genetics Nitric Oxide Synthase Type II / metabolism RAW 264.7 Cells RNA, Double-Stranded / metabolism Respirovirus Infections / immunology* STAT Transcription Factors / metabolism Sendai virus / physiology* Signal Transduction Viral Nonstructural Proteins / metabolism Viral Proteins / genetics Viral Proteins / metabolism*
IF 2.173
Human and Animal Cells RAW 264(RCB0535)