A mosquito salivary protein promotes flavivirus transmission by activation of autophagy
A mosquito salivary protein promotes flavivirus transmission by activation of autophagy
复制标题
DOI：
10.1038/s41467-019-14115-z
复制
发表时间：
2020-01-14
影响因子：
16.6
通讯作者：
Cheng, Gong
中科院分区：
文献类型：
--
作者：
Sun, Peng;Nie, Kaixiao;Cheng, Gong
从受感染的蚊子到宿主的传播是蚊媒黄病毒生命周期中的一个重要过程。许多研究表明，蚊子的唾液有助于病毒传播。在这里，我们发现一种唾液特异性蛋白质，名为埃及伊蚊毒液过敏原-1（AaVA-1），通过激活单核细胞系宿主免疫细胞中的自噬来促进登革热和寨卡病毒的传播。被病毒感染的AaVA-1缺陷型蚊子叮咬的AG 6小鼠（ifnar 1（-/-）ifngr 1（-/-））呈现较低的病毒血症和延长的存活。AaVA-1在细胞内与Beclin-1的显性负性结合物（称为富含亮氨酸的五肽重复序列蛋白（LRPPRC））相互作用，并从LRPPRC介导的隔离中释放Beclin-1，从而启动下游自噬信号传导。Beclin-1的缺乏减少了小鼠中的病毒感染，并消除了AaVA-1介导的蚊子对ZIKV传播的增强。我们的研究为唾液辅助病毒传播提供了一个机制性的见解，并可能为减少黄病毒传播提供一个潜在的预防目标。苔藓唾液影响黄病毒的传播，但其潜在的机制还不完全清楚。在这里，作者表明，埃及伊蚊毒液过敏原-1（AaVA-1）通过激活单核细胞系宿主免疫细胞中的自噬来促进登革热和寨卡病毒的传播。
Transmission from an infected mosquito to a host is an essential process in the life cycle of mosquito-borne flaviviruses. Numerous studies have demonstrated that mosquito saliva facilitates viral transmission. Here we find that a saliva-specific protein, named Aedes aegypti venom allergen-1 (AaVA-1), promotes dengue and Zika virus transmission by activating autophagy in host immune cells of the monocyte lineage. The AG6 mice (ifnar1(-/-)ifngr1(-/-)) bitten by the virus-infected AaVA-1-deficient mosquitoes present a lower viremia and prolonged survival. AaVA-1 intracellularly interacts with a dominant negative binder of Beclin-1, known as leucine-rich pentatricopeptide repeat-containing protein (LRPPRC), and releases Beclin-1 from LRPPRC-mediated sequestration, thereby enabling the initialization of downstream autophagic signaling. A deficiency in Beclin-1 reduces viral infection in mice and abolishes AaVA-1-mediated enhancement of ZIKV transmission by mosquitoes. Our study provides a mechanistic insight into saliva-aided viral transmission and could offer a potential prophylactic target for reducing flavivirus transmission. Mosquito saliva affects transmission of flaviviruses, but underlying mechanisms are incompletely understood. Here, the authors show that Aedes aegypti venom allergen-1 (AaVA-1) promotes dengue and Zika virus transmission by activating autophagy in host immune cells of the monocyte lineage.