@misc{oai:u-fukui.repo.nii.ac.jp:00028702,
 author = {Morita, Naoko and Tanaka, Yukie and Odkhuu, Erdenezaya and Naiki, Yoshikazu and Komatsu, Takayuki and Koide, Naoki},
 month = {Feb},
 note = {Sendai virus V protein is a known antagonist of RIG-I-like receptors (RLRs) RIG-I and MDA5, which activate transcription factors IRF3, leading to activation of ISGF3 and NF-kB. These transcription factors are known activators of inducible NO synthase (iNOS) and increase the production of nitric oxide (NO). By inhibiting ISGF3 and NF-kB, the V protein acts as an indirect negative regulator of iNOS and NO. Here we report that the V gene knockout Sendai virus [SeV V()] markedly enhanced iNOS expression and subsequent NO production in infected macrophages compared to wild-type SeV. The knockout of RIG-I in cells inhibited SeV V()-induced iNOS expression and subsequent NO production. To understand the underlying mechanism of the V protein-mediated negative regulation of iNOS activation, we transfected HEK293T cells with RIG-I and the RIG-I regulatory protein TRIM25. Our results demonstrated that the V protein inhibited iNOS activation via the RIG-I/TRIM25 pathway. Moreover, the V protein inhibited TRIM25-mediated K63-linked ubiquitination of RIG-I, as well as its CARD-dependent interaction with mitochondrial antiviral signaling (MAVS) molecules. These results suggest that the V protein downregulates iNOS activation and inhibits NO production by preventing the RIG-I-MAVS interaction, possibly through its effect on the ubiquitination status of RIG-I.},
 title = {Sendai virus V protein decreases nitric oxide production by inhibiting RIG-I signaling in infected RAW264.7 macrophages},
 year = {2020}
}