Laboratory of Human Retrovirology, Institut de recherches cliniques de Montréal (IRCM) , Montreal, Quebec, Canada.
Department of Cell Biology, University of Alberta , Edmonton, Alberta, Canada.
mBio. 2023 Oct 31;14(5):e0195023. doi: 10.1128/mbio.01950-23. Epub 2023 Sep 29.
In order to efficiently produce infectious viral particles, HIV must counter several restrictions exerted by host cell antiviral proteins. MARCH1 is a member of the MARCH protein family that restricts HIV infection by limiting the incorporation of viral envelope glycoproteins into nascent virions. Here, we identified two regulatory RNAs, microRNAs-25 and -93, induced by the HIV-1 accessory protein Vpu, that downregulate mRNA. We also show that Vpu induces these cellular microRNAs in macrophages by hijacking the cellular β-catenin pathway. The notion that HIV-1 has evolved a mechanism to counteract MARCH1 restriction on viral infectivity underlines the importance of MARCH1 in the host antiviral response.
为了高效产生感染性病毒颗粒，HIV 必须对抗宿主细胞抗病毒蛋白施加的几种限制。MARCH1 是 MARCH 蛋白家族的一员，通过限制病毒包膜糖蛋白掺入新生病毒粒子来限制 HIV 感染。在这里，我们鉴定了两种由 HIV-1 辅助蛋白 Vpu 诱导的调节性 RNA，即 microRNA-25 和 -93，它们下调 mRNA。我们还表明，Vpu 通过劫持细胞 β-连环蛋白途径在巨噬细胞中诱导这些细胞 microRNA。HIV-1 已经进化出一种机制来对抗 MARCH1 对病毒感染力的限制，这突出了 MARCH1 在宿主抗病毒反应中的重要性。
