DENV-2 3′UTR dumbbell structure is a critical factor for viral infection and dissemination in Aedes mosquito

Abstract

Dengue virus (DENV) transmitted by Aedes mosquitoes threatens global health. This study focuses on the dumbbell (DB) structure in DENV-2’s 3′ untranslated region, which is crucial for viral replication and transmission in mosquitoes. We discovered that the absence of the DB structure reduces DENV-2’s replication efficiency and impairs its ability to evade the mosquito midgut barrier. Transcriptome data suggest that the DB structure may facilitate viral escape by modulating the expression of Defensin A and Defensin C. Functional validation in C6/36 cells demonstrates that Defensin C acts as an inhibitor, suppressing the replication of DENV-2 with the absence of DB structure and revealing a novel RNA structure-mediated immune evasion strategy. The findings of this study highlight the critical role of the DB structure in DENV-2 adaptation to mosquito hosts and provide valuable insights into the mechanisms of flavivirus transmission and potential strategies for dengue control.