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

作者：Xiaoyu Wang, Ying Huang, Fei Wang, Qiang Hu, Doudou Huang, Haixia Ma, Yi Liu, Qiyong Liu, Bo Zhang, Zhiming Yuan, Han Xia · 发表于：Journal of Virology · 年份：2025 · DOI：10.1128/jvi.00758-25 · 被引用次数：3 · 研究领域：Mosquito-borne diseases and control、Invertebrate Immune Response Mechanisms、Malaria Research and Control

ABSTRACT Dengue virus (DENV) is a mosquito-borne flavivirus with the capability of replicating and spreading between vertebrate and invertebrate hosts, which poses a huge threat to global public health. Understanding the molecular mechanism of its replication and transmission in mosquitoes is crucial for controlling the dengue epidemic. The 3′ untranslated region (UTR) has been identified as a mediator for viral replication, pathogenicity, and transmission, but its effect on DENV in the mosquito host remains unknown. This study investigated the role of the dumbbell (DB) structure within the 3′UTR of DENV-2 during mosquito infection. The results showed that the absence of the DB structure reduced DENV-2 viral replication efficiency in both mosquito cell lines and Aedes mosquito adults. The DB structure is essential for DENV-2 to escape from the midgut infection and scape barriers, but not for the salivary gland infection and escape barriers. The transcriptome analysis also revealed that the absence of the DB structure increased the expression of Defensin A and Defensin C, which can inhibit viral replication in midgut and spread to hemolymph at 7–10 days post-infection. Through siRNA-mediated knockdown and overexpression experiments in C6/36 cells, we further established that Defensin C exhibits particularly inhibitory effects on the absence of DB structure DENV-2. Our findings highlight the critical role of the DB structure in DENV-2 adaptation to the mosquito host and provide...