TY - JOUR
T1 - Sendai virus C protein limits NO production in infected RAW264.7 macrophages
AU - Odkhuu, Erdenezaya
AU - Komatsu, Takayuki
AU - Koide, Naoki
AU - Naiki, Yoshikazu
AU - Takeuchi, Kenji
AU - Tanaka, Yukie
AU - Tsolmongyn, Bilegtsaikhan
AU - Jambalganiin, Ulziisaikhan
AU - Morita, Naoko
AU - Yoshida, Tomoaki
AU - Gotoh, Bin
AU - Yokochi, Takashi
N1 - Funding Information:
The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This work was supported by a grant from the MEXT-Supported Program for Strategic Research Foundation at Private Universities, 2011–2015 (S1101027) and in part by a KAKENHI Grant-in-Aid for Scientific Research from the Japan Society for the Promotion of Science (C17K08855).
Publisher Copyright:
© The Author(s) 2018.
PY - 2018/10/1
Y1 - 2018/10/1
N2 - 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.
AB - 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.
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U2 - 10.1177/1753425918796619
DO - 10.1177/1753425918796619
M3 - Article
C2 - 30189760
AN - SCOPUS:85054614806
VL - 24
SP - 430
EP - 438
JO - Journal of Endotoxin Research
JF - Journal of Endotoxin Research
SN - 1753-4259
IS - 7
ER -