A mosquito salivary protein promotes flavivirus transmission by activation of autophagy.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 31937766.
- Also identified by DOI 10.1038/s41467-019-14115-z and PMC identifier 6959235.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
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<sup>-/-</sup>ifngr1<sup>-/-</sup>) 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.
Medical subject headings
- Aedes
- Autophagy
- Flavivirus
- Flavivirus Infections
- Insect Proteins
- Mosquito Vectors
- Salivary Proteins and Peptides