| First Author | Sun P | Year | 2020 |
| Journal | Nat Commun | Volume | 11 |
| Issue | 1 | Pages | 260 |
| PubMed ID | 31937766 | Mgi Jnum | J:285921 |
| Mgi Id | MGI:6387763 | Doi | 10.1038/s41467-019-14115-z |
| Citation | Sun P, et al. (2020) A mosquito salivary protein promotes flavivirus transmission by activation of autophagy. Nat Commun 11(1):260 |
| abstractText | 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. |
