Institut Pasteur, Université Paris Cité, CNRS UMR2000, Insect-Virus Interactions Unit, 75015 Paris, France.
Institut Pasteur, Université Paris Cité, CNRS UMR3569, Viruses and RNA Interference Unit, 75015 Paris, France.
Cell Rep. 2023 Aug 29;42(8):112977. doi: 10.1016/j.celrep.2023.112977. Epub 2023 Aug 11.
Arthropod-borne viruses (arboviruses) transmitted by Aedes aegypti mosquitoes are an increasing threat to global health. The small interfering RNA (siRNA) pathway is considered the main antiviral immune pathway of insects, but its effective impact on arbovirus transmission is surprisingly poorly understood. Here, we use CRISPR-Cas9-mediated gene editing in vivo to mutate Dicer2, a gene encoding the RNA sensor and key component of the siRNA pathway. The loss of Dicer2 enhances early viral replication and systemic viral dissemination of four medically significant arboviruses (chikungunya, Mayaro, dengue, and Zika viruses) representing two viral families. However, Dicer2 mutants and wild-type mosquitoes display overall similar levels of vector competence. In addition, Dicer2 mutants undergo significant virus-induced mortality during infection with chikungunya virus. Together, our results define a multifaceted role for Dicer2 in the transmission of arboviruses by Ae. aegypti mosquitoes and pave the way for further mechanistic investigations.
节肢动物传播的病毒（arboviruses）通过埃及伊蚊传播，对全球健康构成日益严重的威胁。小干扰 RNA（siRNA）途径被认为是昆虫的主要抗病毒免疫途径，但 arbovirus 传播的有效影响却出人意料地知之甚少。在这里，我们使用 CRISPR-Cas9 介导的体内基因编辑来突变 Dicer2，该基因编码 RNA 传感器和 siRNA 途径的关键组成部分。Dicer2 的缺失增强了四种具有医学意义的 arboviruses（基孔肯雅热、马亚罗、登革热和寨卡病毒）的早期病毒复制和全身病毒传播，这四种 arboviruses 代表了两个病毒家族。然而，Dicer2 突变体和野生型蚊子表现出总体相似的媒介能力。此外，Dicer2 突变体在感染基孔肯雅热病毒时会发生显著的病毒诱导死亡。总之，我们的结果定义了 Dicer2 在埃及伊蚊传播 arboviruses 中的多方面作用，并为进一步的机制研究铺平了道路。
