| First Author | Jin L | Year | 2018 |
| Journal | Nat Immunol | Volume | 19 |
| Issue | 4 | Pages | 342-353 |
| PubMed ID | 29507355 | Mgi Jnum | J:282381 |
| Mgi Id | MGI:6380759 | Doi | 10.1038/s41590-018-0063-9 |
| Citation | Jin L, et al. (2018) Salivary factor LTRIN from Aedes aegypti facilitates the transmission of Zika virus by interfering with the lymphotoxin-beta receptor. Nat Immunol 19(4):342-353 |
| abstractText | Pathogens have co-evolved with mosquitoes to optimize transmission to hosts. Mosquito salivary-gland extract is known to modulate host immune responses and facilitate pathogen transmission, but the underlying molecular mechanisms of this have remained unknown. In this study, we identified and characterized a prominent 15-kilodalton protein, LTRIN, obtained from the salivary glands of the mosquito Aedes aegypti. LTRIN expression was upregulated in blood-fed mosquitoes, and LTRIN facilitated the transmission of Zika virus (ZIKV) and exacerbated its pathogenicity by interfering with signaling through the lymphotoxin-beta receptor (LTbetaR). Mechanically, LTRIN bound to LTbetaR and 'preferentially' inhibited signaling via the transcription factor NF-kappaB and the production of inflammatory cytokines by interfering with the dimerization of LTbetaR during infection with ZIKV. Furthermore, treatment with antibody to LTRIN inhibited mosquito-mediated infection with ZIKV, and abolishing LTbetaR potentiated the infectivity of ZIKV both in vitro and in vivo. This study provides deeper insight into the transmission of mosquito-borne diseases in nature and supports the therapeutic potential of inhibiting the action of LTRIN to disrupt ZIKV transmission. |
