From the Department of Pathology, National Institute of Infectious Diseases, Tokyo 162-8640, Japan.
the Faculty of Life and Environmental Sciences, University of Yamanashi, Yamanashi 400-8510, Japan.
J Biol Chem. 2019 Mar 8;294(10):3397-3405. doi: 10.1074/jbc.AC118.005907. Epub 2019 Jan 10.
Membrane-associated RING-CH 8 (MARCH8) is one of 11 members of the MARCH family of RING finger E3 ubiquitin ligases and down-regulates several membrane proteins ( major histocompatibility complex II [MHC-II], CD86, and transferrin receptor). We recently reported that MARCH8 also targets HIV-1 envelope glycoproteins and acts as an antiviral factor. However, it remains unclear whether other family members might have antiviral functions similar to those of MARCH8. Here we show that MARCH1 and MARCH2 are MARCH family members that reduce virion incorporation of envelope glycoproteins. Infectivity assays revealed that MARCH1 and MARCH2 dose-dependently suppress viral infection. Treatment with type I interferon enhanced endogenous expression levels of MARCH1 and MARCH2 in monocyte-derived macrophages. Expression of these proteins in virus-producing cells decreased the efficiency of viral entry and down-regulated HIV-1 envelope glycoproteins from the cell surface, resulting in reduced incorporation of envelope glycoproteins into virions, as observed in MARCH8 expression. With the demonstration that MARCH1 and MARCH2 are antiviral MARCH family members as presented here, these two proteins join a growing list of host factors that inhibit HIV-1 infection.
膜相关环指蛋白 8（MARCH8）是 RING 指 E3 泛素连接酶家族的 11 个成员之一，可下调几种膜蛋白（主要组织相容性复合体 II [MHC-II]、CD86 和转铁蛋白受体）。我们最近报道 MARCH8 还靶向 HIV-1 包膜糖蛋白并作为抗病毒因子。然而，其他家族成员是否具有类似于 MARCH8 的抗病毒功能尚不清楚。在这里，我们表明 MARCH1 和 MARCH2 是降低包膜糖蛋白病毒粒子掺入的 MARCH 家族成员。感染性测定显示 MARCH1 和 MARCH2 以剂量依赖性方式抑制病毒感染。用 I 型干扰素处理可增强单核细胞来源的巨噬细胞中内源性 MARCH1 和 MARCH2 的表达水平。在产生病毒的细胞中表达这些蛋白可降低病毒进入的效率，并下调细胞表面的 HIV-1 包膜糖蛋白，从而减少包膜糖蛋白掺入病毒粒子中，这与 MARCH8 表达的情况一致。如这里所示，MARCH1 和 MARCH2 是抗病毒的 MARCH 家族成员，这两种蛋白加入了越来越多的抑制 HIV-1 感染的宿主因子。
