Couderc Elodie, Crist Anna B, Daron Josquin, Varet Hugo, van Hout Femke A H, Miesen Pascal, Palatini Umberto, Dabo Stéphanie, Vial Thomas, Lambrechts Louis, Merkling Sarah H
Institut Pasteur, Université Paris Cité, CNRS UMR2000, Insect-Virus Interactions Unit, Paris, 75015, France.
Sorbonne Université, Collège Doctoral, Paris, 75005, France.
BMC Biol. 2025 Jul 28;23(1):223. doi: 10.1186/s12915-025-02325-5.
Arthropod-borne viruses (arboviruses) such as dengue virus (DENV) and Zika virus (ZIKV) pose a significant threat to global health. Novel approaches to control the spread of arboviruses focus on harnessing the antiviral immune system of their primary vector, the Aedes aegypti mosquito. In arthropods, genes of the Vago family are often presented as analogs of mammalian cytokines with potential antiviral functions, but the role of Vago genes upon virus infection in Ae. aegypti is largely unknown.
We conducted a phylogenetic analysis of the Vago gene family in Diptera, which led us to focus on a Vago-like gene that we named VLG-1. Using CRISPR/Cas9-mediated gene editing, we generated a VLG-1 mutant line of Ae. aegypti, which revealed a broad impact of VLG-1 on the mosquito transcriptome, affecting several biological processes potentially related to viral replication, including the oxidative stress response. Surprisingly, experimental viral challenge of the VLG-1 mutant line indicated a modest proviral role for this gene during DENV and ZIKV infections in vivo. In the absence of VLG-1, virus dissemination throughout the mosquito's body was slightly impaired, albeit not altering virus transmission rates.
Our results challenge the conventional understanding of Vago-like genes as antiviral factors and underscore the need for further in vivo research to elucidate the molecular mechanisms underlying mosquito-arbovirus interactions.
登革热病毒（DENV）和寨卡病毒（ZIKV）等节肢动物传播病毒（虫媒病毒）对全球健康构成重大威胁。控制虫媒病毒传播的新方法聚焦于利用其主要传播媒介埃及伊蚊的抗病毒免疫系统。在节肢动物中，Vago家族基因常被视为具有潜在抗病毒功能的哺乳动物细胞因子类似物，但Vago基因在埃及伊蚊病毒感染中的作用很大程度上尚不清楚。
我们对双翅目昆虫的Vago基因家族进行了系统发育分析，这使我们聚焦于一个类似Vago的基因，我们将其命名为VLG-1。利用CRISPR/Cas9介导的基因编辑技术，我们构建了埃及伊蚊的VLG-1突变品系，该品系揭示了VLG-1对蚊子转录组有广泛影响，影响了几个可能与病毒复制相关的生物学过程，包括氧化应激反应。令人惊讶的是，对VLG-1突变品系进行的实验性病毒攻击表明，该基因在登革热病毒和寨卡病毒体内感染期间具有适度的前病毒作用。在没有VLG-1的情况下，病毒在蚊子体内的传播略有受损，尽管没有改变病毒传播率。
我们的结果挑战了将类似Vago基因视为抗病毒因子的传统认识，并强调需要进一步开展体内研究，以阐明蚊子与虫媒病毒相互作用的分子机制。
