Department of Microbiology and Immunology, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, Buffalo, New York, USA.
Department of Microbiology and Immunology, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, Buffalo, New York, USA
mBio. 2021 Mar 2;12(2):e03264-20. doi: 10.1128/mBio.03264-20.
The membrane-associated RING-CH (MARCH) proteins belong to a family of E3 ubiquitin ligases, whose main function is to remove transmembrane proteins from the plasma membrane. Recent work has shown that the human MARCH1, 2, and 8 are antiretroviral factors that target the human immunodeficiency virus type 1 (HIV-1) envelope glycoproteins by reducing their incorporation in the budding virions. Nevertheless, the dearth of information regarding the antiviral mechanism of this family of proteins necessitates further examination. In this study, using both the human MARCH proteins and their mouse homologues, we provide a comprehensive analysis of the antiretroviral mechanism of this family of proteins. Moreover, we show that human MARCH proteins restrict to various degrees the envelope glycoproteins of a diverse number of viruses. This report sheds light on the important antiviral function of MARCH proteins and their significance in cell intrinsic immunity. This study examines the mechanism utilized by different MARCH proteins to restrict retrovirus infection. MARCH proteins block the incorporation of envelope glycoproteins to the budding virions. In this report, by comparing the human and mouse MARCH genes and using murine leukemia virus (MLV) and HIV-1, we identify differences in the mechanism of restriction among MARCH proteins. Furthermore, we perform a comprehensive analysis on a number of envelope glycoproteins and show that MARCH proteins have broad antiviral functions.
膜相关环指(MARCH)蛋白属于 E3 泛素连接酶家族,其主要功能是将跨膜蛋白从质膜上移除。最近的研究表明,人类 MARCH1、2 和 8 是抗逆转录病毒因子,通过减少 HIV-1 包膜糖蛋白在出芽病毒粒子中的掺入,靶向人类免疫缺陷病毒 1(HIV-1)包膜糖蛋白。然而,由于缺乏关于该蛋白家族抗病毒机制的信息,需要进一步研究。在这项研究中,我们使用人类 MARCH 蛋白及其小鼠同源物,对该蛋白家族的抗病毒机制进行了全面分析。此外,我们还表明人类 MARCH 蛋白在不同程度上限制了多种病毒的包膜糖蛋白。本报告阐明了 MARCH 蛋白的重要抗病毒功能及其在细胞固有免疫中的意义。本研究探讨了不同 MARCH 蛋白限制逆转录病毒感染所利用的机制。MARCH 蛋白阻止包膜糖蛋白掺入出芽病毒粒子。在本报告中,通过比较人类和小鼠 MARCH 基因,并使用鼠白血病病毒(MLV)和 HIV-1,我们确定了 MARCH 蛋白在限制机制方面的差异。此外,我们对多种包膜糖蛋白进行了全面分析,表明 MARCH 蛋白具有广泛的抗病毒功能。