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Background <p>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 <i>Aedes aegypti</i> mosquito. In arthropods, genes of the <i>Vago</i> family are often presented as analogs of mammalian cytokines with potential antiviral functions, but the role of <i>Vago</i> genes upon virus infection in <i>Ae. aegypti</i> is largely unknown.</p> Results <p>We conducted a phylogenetic analysis of the <i>Vago</i> gene family in Diptera, which led us to focus on a <i>Vago</i>-like gene that we named <i>VLG-1</i>. Using CRISPR/Cas9-mediated gene editing, we generated a <i>VLG-1</i> mutant line of <i>Ae. aegypti</i>, which revealed a broad impact of <i>VLG-1</i> on the mosquito transcriptome, affecting several biological processes potentially related to viral replication, including the oxidative stress response. Surprisingly, experimental viral challenge of the <i>VLG-1</i> mutant line indicated a modest proviral role for this gene during DENV and ZIKV infections in vivo. In the absence of <i>VLG-1</i>, virus dissemination throughout the mosquito’s body was slightly impaired, albeit not altering virus transmission rates.</p> Conclusions <p>Our results challenge the conventional understanding of <i>Vago</i>-like genes as antiviral factors and underscore the need for further in vivo research to elucidate the molecular mechanisms underlying mosquito-arbovirus interactions.</p>

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Aedes aegypti VLG-1 challenges the assumed antiviral nature of Vago genes

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年7月28日

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  • Elodie Couderc,
  • Anna B. Crist,
  • Josquin Daron,
  • Hugo Varet,
  • Femke A. H. van Hout,
  • Pascal Miesen,
  • Umberto Palatini,
  • Stéphanie Dabo,
  • Thomas Vial,
  • Louis Lambrechts,
  • Sarah H. Merkling

摘要

Background

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.

Results

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.

Conclusions

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.