A mosquito salivary protein promotes flavivirus transmission by activation of autophagy

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

Research output: Contribution to journalArticlepeer-review

10 Scopus citations

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.

Original languageEnglish (US)
Article number260
JournalNature communications
Volume11
Issue number1
DOIs
StatePublished - Dec 1 2020
Externally publishedYes

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

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