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A mosquito salivary protein promotes flavivirus transmission by activation of autophagy

Author

Listed:
  • Peng Sun

    (Tsinghua University
    Shenzhen Center for Disease Control and Prevention)

  • Kaixiao Nie

    (Tsinghua University)

  • Yibin Zhu

    (Tsinghua University
    Shenzhen Center for Disease Control and Prevention
    Tsinghua University)

  • Yang Liu

    (Tsinghua University
    Tsinghua University)

  • Pa Wu

    (Tsinghua University)

  • Ziwen Liu

    (Tsinghua University)

  • Senyan Du

    (Tsinghua University)

  • Huahao Fan

    (Tsinghua University)

  • Chun-Hong Chen

    (National Health Research Institutes, Zhunan)

  • Renli Zhang

    (Shenzhen Center for Disease Control and Prevention)

  • Penghua Wang

    (The University of Connecticut Health Center)

  • Gong Cheng

    (Tsinghua University
    Shenzhen Center for Disease Control and Prevention)

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.

Suggested Citation

  • 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, 2020. "A mosquito salivary protein promotes flavivirus transmission by activation of autophagy," Nature Communications, Nature, vol. 11(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-019-14115-z
    DOI: 10.1038/s41467-019-14115-z
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