GAPDH mediates plant reovirus-induced incomplete autophagy for persistent viral infection in leafhopper vector
GAPDH mediates plant reovirus-induced incomplete autophagy for persistent viral infection in leafhopper vector
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DOI：
10.1080/15548627.2022.2115830
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发表时间：
2022-08-29
期刊：
影响因子：
13.3
通讯作者：
Wei, Taiyun
中科院分区：
文献类型：
--
作者：
Chen, Qian;Zhang, Yuele;Wei, Taiyun
自噬（Macroautophagy/autophagy）是宿主生物体为抵抗病毒感染而启动的一种保守机制。双膜自噬体在节肢动物载体中可以被虫媒病毒重塑以容纳病毒体并促进病毒持续繁殖，但其潜在机制尚不清楚。水稻瘤矮病毒（RGDV）是一种无包膜的双链RNA病毒，能诱导含有病毒的双膜自噬体的形成，有利于病毒在叶蝉载体中的持续繁殖。在这项研究中，发现RGDV的衣壳蛋白P2单独诱导自噬。在体外和体内，P2特异性地与GAPDH（甘油醛-3-磷酸脱氢酶）和ATG 4 B相互作用。此外，GAPDH-ATG 4 B复合物可以被招募到病毒诱导的自噬体中。GAPDH或ATG 4 B表达的沉默抑制ATG 8脂化、自噬体形成和有效的病毒繁殖。因此，P2可以直接募集GAPDH-ATG 4 B复合物以诱导初始自噬体的形成。此外，这种自噬体被修饰以避免与溶酶体融合以进行降解，因此可以被病毒持续利用以促进有效繁殖。GAPDH与ATG 14结合并抑制ATG 14与SNAP 29的相互作用，从而阻止ATG 14-SNARE蛋白介导自噬体-溶酶体融合。总之，这些结果突出了RGDV如何激活GAPDH以启动自噬体形成并阻断自噬体降解，最终促进昆虫载体中的持续病毒繁殖。这些发现揭示了在病毒感染期间昆虫媒介中的免疫应答的正调节。
Macroautophagy/autophagy is a conserved mechanism launched by host organisms to fight against virus infection. Double-membraned autophagosomes in arthropod vectors can be remodeled by arboviruses to accommodate virions and facilitate persistent viral propagation, but the underlying mechanism is unknown. Rice gall dwarf virus (RGDV), a plant nonenveloped double-stranded RNA virus, induces the formation of virus-containing double-membraned autophagosomes to benefit persistent viral propagation in leafhopper vectors. In this study, it was found that the capsid protein P2 of RGDV alone induced autophagy. P2 specifically interacted with GAPDH (glyceraldehyde-3-phosphate dehydrogenase) and ATG4B both in vitro and in vivo. Furthermore, the GAPDH-ATG4B complex could be recruited to virus-induced autophagosomes. Silencing of GAPDH or ATG4B expression suppressed ATG8 lipidation, autophagosome formation, and efficient viral propagation. Thus, P2 could directly recruit the GAPDH-ATG4B complex to induce the formation of initial autophagosomes. Furthermore, such autophagosomes were modified to evade fusion with lysosomes for degradation, and thus could be persistently exploited by viruses to facilitate efficient propagation. GAPDH bound to ATG14 and inhibited the interaction of ATG14 with SNAP29, thereby preventing ATG14-SNARE proteins from mediating autophagosome-lysosome fusion. Taken together, these results highlight how RGDV activates GAPDH to initiate autophagosome formation and block autophagosome degradation, finally facilitating persistent viral propagation in insect vectors. The findings reveal a positive regulation of immune response in insect vectors during viral infection.