Sendai virus C protein affects macrophage function, which plays a critical role in modulating disease severity during Sendai virus infection in mice
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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DOI：
10.1111/1348-0421.12956
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发表时间：
2022-01-03
影响因子：
2.6
通讯作者：
Komatsu, Takayuki
中科院分区：
文献类型：
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作者：
Sakuma, Ryusuke;Morita, Naoko;Komatsu, Takayuki
仙台病毒(SeV)辅助蛋白C在病毒转录和复制过程中限制双链RNA或缺陷干扰RNA的产生，从而限制β干扰素的产生。我们最近对小鼠巨噬细胞系的体外分析表明，该蛋白还有助于限制巨噬细胞的功能，包括在感染的巨噬细胞中产生一氧化氮(NO)和炎症细胞因子，以及干扰素-β。本研究表明，在重组C基因敲除SeV(SeV Increment C)感染的小鼠中，氯屈膦酸脂质体耗尽呼吸道巨噬细胞可导致严重的病毒性肺炎，但不能调节野生型SeV感染小鼠的病情严重程度。此外，在巨噬细胞耗尽、SeV增加的C感染小鼠中观察到的严重疾病与肺部病毒复制加剧有关，导致严重的呼吸道炎症和肺水肿，表明肺损伤。提示SeV C蛋白的抗巨噬细胞活性可能在调节SeV引起的肺损伤及相关疾病中起重要作用。
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-beta 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-beta, 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 (SeV increment C)-infected mice, but did not modulate disease severity in wild-type SeV-infected mice. Furthermore, the severe disease observed in macrophage-depleted, SeV increment C-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.