A mosquito salivary protein promotes flavivirus transmission by activation of autophagy.

Abstract	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.
Authors	Peng Sun, Kaixiao Nie, Yibin Zhu, Yang Liu, Pa Wu, Ziwen Liu, Senyan Du, Huahao Fan, Chun-Hong Chen, Renli Zhang, Penghua Wang, Gong Cheng
Journal	Nature communications (Nat Commun) Vol. 11 Issue 1 Pg. 260 (01 14 2020) ISSN: 2041-1723 [Electronic] England
PMID	31937766 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References	Beclin-1 Becn1 protein, mouse Insect Proteins Lrpprc protein, mouse Neoplasm Proteins Salivary Proteins and Peptides
Topics	Aedes (metabolism, virology) Animals Autophagy Beclin-1 (deficiency, metabolism) Dengue Virus (physiology) Flavivirus (physiology) Flavivirus Infections (transmission, virology) Humans Insect Proteins (deficiency, genetics, metabolism) Mice Mosquito Vectors (metabolism, virology) Neoplasm Proteins (metabolism) Protein Binding Salivary Proteins and Peptides (deficiency, genetics, metabolism) THP-1 Cells Virus Replication Zika Virus (physiology)

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