@article{10272d4be45b4934bae853d274238de4,
title = "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.",
author = "Peng Sun and Kaixiao Nie and Yibin Zhu and Yang Liu and Pa Wu and Ziwen Liu and Senyan Du and Huahao Fan and Chen, {Chun Hong} and Renli Zhang and Penghua Wang and Gong Cheng",
note = "Funding Information: We thank Professor Liang Ge from Tsinghua University School of Life Sciences to provide suggestions for the autophagy studies. We thank Professor Qiyong Liu from China CDC to donate the A. albopictus Jiangsu strain. This work was funded by the grants from the National Key Research and Development Plan of China (2019YFC1200201, 2018YFA0507202, 2018ZX09711003-004-003, 2016ZX10004001-008, 2016YFC1201000, and 2016YFD0500400), the National Natural Science Foundation of China (81730063, 31825001, and 815719754), and Shenzhen San-Ming Project for prevention and research on vector-borne diseases (SZSM201611064). We thank the core facilities of the Center for Life Sciences and Center of Biomedical Analysis for technical assistance (Tsinghua University). Funding Information: 4National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Zhunan, Miaoli, Taiwan 35053, China. 5Department of Immunology, School of Medicine, The University of Connecticut Health Center, Farmington, Connecticut 06030, USA. 6These authors contributed equally: Peng Sun, Kaixiao Nie. *email: gongcheng@mail.tsinghua.edu.cn Publisher Copyright: {\textcopyright} 2020, The Author(s).",
year = "2020",
month = dec,
day = "1",
doi = "10.1038/s41467-019-14115-z",
language = "English (US)",
volume = "11",
journal = "Nature Communications",
issn = "2041-1723",
publisher = "Nature Publishing Group",
number = "1",
}