Sendai virus V protein decreases nitric oxide production by inhibiting RIG-I signaling in infected RAW264.7 macrophages

Morita, Naoko; Tanaka, Yukië; Odkhuu, Erdenezaya; Naiki, Yoshikazu; Komatsu, Takayuki; Koide, Naoki

doi:10.1016/j.micinf.2020.01.005

Cited by 7 publications

(11 citation statements)

References 35 publications

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“…The cDNA fragment encoding mouse RIG-I protein [1-926 aa] or mutant mouse RIG-I protein RIG-IC [231-926 aa] was used as previously described ( Morita et al, 2020 ). The expression plasmid for RIG-I or RIG-IC with EGFP tag was created using the multicloning site of pCA7 with N-terminal EGFP tag by insertion of the cDNA fragment.…”

Section: Methodsmentioning

confidence: 99%

“…Membrane Ruffling in RAW264.7 Macrophages Infected With 4C(−) SeV 4C(−) has been reported to produce dsRNA during viral transcription and replication, thereby inducing IFN-β, possibly via the RIG-I pathway (Takeuchi et al, 2008;Odkhuu et al, 2018;Morita et al, 2020). To investigate the role of dsRNA in membrane ruffle formation and phagocytosis, we attempted to isolate and characterize a new SeV C mutant from the 4C(−) strain that does not generate dsRNA.…”

Section: Role Of Dsrna In Phagocytosis Andmentioning

confidence: 99%

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SeV C Protein Plays a Role in Restricting Macrophage Phagocytosis by Limiting the Generation of Intracellular Double-Stranded RNA

et al. 2022

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Macrophages play a central role in the innate immune response to respiratory viral infections through pro-inflammatory factor secretion and phagocytosis. However, as a countermeasure, viral pathogens have evolved virulence factors to antagonize macrophage function. In our recent in vitro analyses of murine macrophage cell lines, Sendai virus (SeV) accessory protein C inhibited the secretion of pro-inflammatory factors, and C gene-knockout SeV (SeVΔC) caused drastic morphological changes in RAW264.7 macrophages, similar to those observed after stimulation with Lipid A, a well-known activator of actin-rich membrane ruffle formation and phagocytosis. Hence, we sought to determine whether the C protein limits phagocytosis in SeV-infected macrophages through the suppression of membrane ruffling. Phagocytosis assays indicated an upregulation of phagocytosis in both SeVΔC-infected and Lipid A-stimulated macrophages, but not in SeV WT-infected cells. Further, the observed membrane ruffling was associated with phagocytosis. RIG-I is essential for Lipid A-induced phagocytosis; its deficiency inhibited SeVΔC-stimulated phagocytosis and ruffling, confirming the essential role of RIG-I. Moreover, treatment with interferon (IFN)-β stimulation and neutralizing antibodies against IFN-β suggested that SeVΔC-induced phagocytosis and ruffling occurred in an IFN-β-independent manner. A newly isolated SeVΔC strain that does not generate dsRNA further highlighted the importance of dsRNA in the induction of phagocytosis and ruffling. Taken together, the current results suggest that SeV C protein might limit phagocytosis-associated membrane ruffling in an RIG-I-mediated but IFN-independent manner via limiting the generation of intracellular dsRNA.

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Section: Methodsmentioning

confidence: 99%

Section: Role Of Dsrna In Phagocytosis Andmentioning

confidence: 99%

SeV C Protein Plays a Role in Restricting Macrophage Phagocytosis by Limiting the Generation of Intracellular Double-Stranded RNA

et al. 2022

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“…Recently, SeV V protein was demonstrated to inhibit TRIM25-mediated ubiquitination of RIG-I. Meanwhile, SeV V also suppresses the CARD-dependent interaction between RIG-I and MAVS, thus preventing the iNOS activation and NO production (Morita et al, 2020). Sánchez-Aparicio et al (2018) found that V proteins of some paramyxoviruses (including MeV, SeV, NiV, and PIV5) could bind to the CARD domain of RIG-I and prevent the downstream RIG-I-mediated signaling.…”

Section: Rig-i Mda5 and Lgp2mentioning

confidence: 99%

Evasion of Host Antiviral Innate Immunity by Paramyxovirus Accessory Proteins

Wang

Duan

et al. 2022

Front. Microbiol.

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For efficient replication, viruses have developed multiple strategies to evade host antiviral innate immunity. Paramyxoviruses are a large family of enveloped RNA viruses that comprises diverse human and animal pathogens which jeopardize global public health and the economy. The accessory proteins expressed from the P gene by RNA editing or overlapping open reading frames (ORFs) are major viral immune evasion factors antagonizing type I interferon (IFN-I) production and other antiviral innate immune responses. However, the antagonistic mechanisms against antiviral innate immunity by accessory proteins differ among viruses. Here, we summarize the current understandings of immune evasion mechanisms by paramyxovirus accessory proteins, specifically how accessory proteins directly or indirectly target the adaptors in the antiviral innate immune signaling pathway to facilitate virus replication. Additionally, some cellular responses, which are also involved in viral replication, will be briefly summarized.

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“…14,15 Further research showed that C proteins limit the generation of dsRNAs during viral transcription and replication, thereby limiting the activation of the retinoic acid-inducible gene I (RIG-I) pathway that leads to the activation of transcription factor interferon regulatory factor 3 (IRF3) and nuclear factor-kappa-light-chainenhancer of activated B cells (NF-κB), ultimately leading to the activation of interferon stimulated gene factor 3 (ISGF3). 13,16 ISGF3, NF-κB, or both, are known activators that increase the production of NO and a variety of cytokines in macrophages. 17 Macrophages secrete NO and various cytokines, orchestrate the adaptive immune system, and clear infected and dying cells to aid host recovery.…”

Section: Introductionmentioning

confidence: 99%

Sendai virus C protein affects macrophage function, which plays a critical role in modulating disease severity during Sendai virus infection in mice

Sakuma

Morita

Tanaka

et al. 2022

Microbiology and Immunology

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Sendai virus (SeV) accessory protein C limits the generation of double-stranded RNAs, defective interfering RNAs, or both, during viral transcription and replication, thereby limiting interferon-β production. Our recent in vitro analyses on murine macrophage cell lines demonstrated that this protein also contributes to restricting macrophage function, including the production of nitric oxide (NO) and inflammatory cytokines in addition to interferon-β, in infected macrophages. This study showed that depletion of airway macrophages by clodronate-loaded liposomes led to the development of severe viral pneumonia in recombinant C gene-knockout SeV (SeVΔC)-infected mice, but did not modulate disease severity in wild-type SeVinfected mice. Furthermore, the severe disease observed in macrophage-depleted, SeVΔC-infected mice was associated with exacerbated virus replication in the lungs, leading to severe airway inflammation and pulmonary edema, indicating lung injury. These results suggested that the antimacrophage activity of SeV C protein might play a critical role in modulating lung injury and associated diseases caused by SeV.

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Sendai virus V protein decreases nitric oxide production by inhibiting RIG-I signaling in infected RAW264.7 macrophages

Cited by 7 publications

References 35 publications

SeV C Protein Plays a Role in Restricting Macrophage Phagocytosis by Limiting the Generation of Intracellular Double-Stranded RNA

SeV C Protein Plays a Role in Restricting Macrophage Phagocytosis by Limiting the Generation of Intracellular Double-Stranded RNA

Evasion of Host Antiviral Innate Immunity by Paramyxovirus Accessory Proteins

Sendai virus C protein affects macrophage function, which plays a critical role in modulating disease severity during Sendai virus infection in mice

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