State Key Laboratory of Virology, School of Public Health, Wuhan University, Wuhan, China.
Nhc Key laboratory of Enteric Pathogenic Microbiology, Jiangsu Provincial Center for Disease Control and Prevention, Nanjing, China, Nanjing, China.
Autophagy. 2022 Jul;18(7):1599-1612. doi: 10.1080/15548627.2021.1994296. Epub 2021 Nov 6.
Severe fever with thrombocytopenia syndrome virus (SFTSV) is an emerging negatively stranded enveloped RNA bunyavirus that causes SFTS with a high case fatality rate of up to 30%. Macroautophagy/autophagy is an evolutionarily conserved process involved in the maintenance of host homeostasis, which exhibits anti-viral or pro-viral responses in reaction to different viral challenges. However, the interaction between the bunyavirus SFTSV and the autophagic process is still largely unclear. By establishing various autophagy-deficient cell lines, we found that SFTSV triggered RB1CC1/FIP200-BECN1-ATG5-dependent classical autophagy flux. SFTSV nucleoprotein induced BECN1-dependent autophagy by disrupting the BECN1-BCL2 association. Importantly, SFTSV utilized autophagy for the viral life cycle, which not only assembled in autophagosomes derived from the ERGIC and Golgi complex, but also utilized autophagic vesicles for exocytosis. Taken together, our results suggest a novel virus-autophagy interaction model in which bunyavirus SFTSV induces classical autophagy flux for viral assembly and egress processes, suggesting that autophagy inhibition may be a novel therapy for treating or releasing SFTS.
严重发热伴血小板减少综合征病毒（SFTSV）是一种新兴的负链包膜 RNA 布尼亚病毒，可引起 SFTS，其病死率高达 30%。巨自噬/自噬是一种进化上保守的过程，参与维持宿主内环境平衡，它在应对不同的病毒挑战时表现出抗病毒或促病毒反应。然而，布尼亚病毒 SFTSV 与自噬过程之间的相互作用在很大程度上仍不清楚。通过建立各种自噬缺陷细胞系，我们发现 SFTSV 触发 RB1CC1/FIP200-BECN1-ATG5 依赖性经典自噬流。SFTSV 核蛋白通过破坏 BECN1-BCL2 结合来诱导 BECN1 依赖性自噬。重要的是，SFTSV 利用自噬进行病毒生命周期，它不仅在源自 ERGIC 和高尔基体复合物的自噬体中组装，而且还利用自噬小泡进行胞吐作用。总之，我们的研究结果表明了一种新的病毒-自噬相互作用模型，其中布尼亚病毒 SFTSV 诱导经典自噬流用于病毒组装和出芽过程，这表明自噬抑制可能是治疗或释放 SFTS 的一种新疗法。
