Sendai virus C protein limits NO production in infected RAW264.7 macrophages

Erdenezaya Odkhuu, Takayuki Komatsu, Naoki Koide, Yoshikazu Naiki, Kenji Takeuchi, Yukie Tanaka, Bilegtsaikhan Tsolmongyn, Ulziisaikhan Jambalganiin, Naoko Morita, Tomoaki Yoshida, Bin Gotoh, Takashi Yokochi

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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.

Original languageEnglish
Pages (from-to)430-438
Number of pages9
JournalInnate Immunity
Volume24
Issue number7
DOIs
Publication statusPublished - 01-10-2018

All Science Journal Classification (ASJC) codes

  • Microbiology
  • Immunology
  • Molecular Biology
  • Cell Biology
  • Infectious Diseases

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    Odkhuu, E., Komatsu, T., Koide, N., Naiki, Y., Takeuchi, K., Tanaka, Y., Tsolmongyn, B., Jambalganiin, U., Morita, N., Yoshida, T., Gotoh, B., & Yokochi, T. (2018). Sendai virus C protein limits NO production in infected RAW264.7 macrophages. Innate Immunity, 24(7), 430-438. https://doi.org/10.1177/1753425918796619