A novel viral regulatory network for autophagy induction: Respiratory Syncytial Virus NS2 protein regulates autophagy by modulating BECN1 ISGylation and protein stability.
A novel viral regulatory network for autophagy induction: Respiratory Syncytial Virus NS2 protein regulates autophagy by modulating BECN1 ISGylation and protein stability.
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DOI：
10.1080/27694127.2022.2076769
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发表时间：
2022
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呼吸道合胞病毒（RSV）是儿童和其他易感人群中病毒性肺炎和细支气管炎的主要原因。RSV感染使免疫反应失调，导致气道炎症加剧。在其他应答中，RSV诱导巨自噬/自噬，这是在感染期间调节免疫应答的关键过程。我们研究了RSV诱导的自噬的分子机制，并表明RSV非结构性NS 2蛋白使用双重机制促进自噬。首先，NS 2与自噬调节因子BECN 1（beclin 1）相互作用并稳定自噬调节因子BECN 1，增加其细胞内自噬诱导的可用性。其次，NS 2干扰BECN 1 ISG化，从而限制BECN 1的抗自噬ISG化形式的细胞内库。因此，病毒蛋白（即，NS 2）-自噬-ISG化轴代表了一种未知的病毒调控网络。由于许多病毒诱导自噬，形成病毒相关的免疫反应，包括炎症，探索病毒蛋白自噬-ISGylation调控网络可以帮助开发干预措施，以抑制过度的免疫反应，如炎症，用于治疗病毒相关的炎性疾病。
Respiratory syncytial virus, or RSV, is a leading cause of viral pneumonia and bronchiolitis in children and other susceptible populations. RSV infection dysregulates the immune response leading to exaggerated inflammation in the airway. Among other responses, RSV induces macroautophagy/autophagy, a key process that regulates immune response during infection. We investigated the molecular mechanisms underlying RSV-induced autophagy and showed that the RSV nonstructural NS2 protein promotes autophagy using a dual mechanism. First, NS2 interacts with and stabilizes the autophagy regulator BECN1 (beclin 1), augmenting its intracellular availability for autophagy induction. Second, NS2 interferes with BECN1 ISGylation, thus restricting the intracellular pool of the anti-autophagy ISGylated form of BECN1. Thus, the viral protein (i.e., NS2)-autophagy-ISGylation axis represents a yet unknown regulatory network for viruses. As many viruses induce autophagy that shapes virus-associated immune responses including inflammation, exploring viral protein-autophagy-ISGylation regulatory networks can aid in developing interventions to curb exaggerated immune responses such as inflammation for treating virus-associated inflammatory diseases.