Tetherin/BST-2 Is Essential for the Formation of the Intracellular Virus-Containing Compartment in HIV-Infected Macrophages

• Type of Material: Article
• Authors: Hin Chu, Emory University; Jaang-Jiun Wang, Emory University; Mingli Qi, Emory University; Jeong-Joong Yoon, Emory University; Xuemin Chen, Emory University; Xiaoyun Wen, Emory University; Jason Edward Hammonds, Emory University; Lingmei Ding, Emory University; Paul Spearman, Emory University
• Language: English
• Date: 2012-09-13
• Publisher: Elsevier (Cell Press)
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2012 Elsevier Inc.
• License: Creative Commons Attribution-NonCommerical-NoDerivs 3.0 Unported
• Final Published Version (URL): http://dx.doi.org/10.1016/j.chom.2012.07.011
• Title of Journal or Parent Work: Cell Host and Microbe
• ISSN: 1931-3128
• Volume: 12
• Issue: 3
• Start Page: 360
• End Page: 372
• Grant/Funding Information: The work was partly supported by the flow cytometry/cell sorting core of Children’s Healthcare of Atlanta, by the Emory Center for AIDS Research (P30 AI050409), and by the Robert P. Apkarian Integrated Electron Microscopy Core Laboratory of Emory University.; This work was supported by NIH AI058828 and NIH AI40338 and by funds from Children’s Healthcare of Atlanta.
• Research Categories: Biology, Virology; Biology, Cell; Health Sciences, General

Abstract

HIV-1 assembly and release occurs at the plasma membrane in T lymphocytes, while intracellular sites of virus assembly or accumulation are apparent in macrophages. The host protein tetherin (BST-2) inhibits HIV release from the plasma membrane by retaining viral particles at the cell surface, but the role of tetherin at intracellular HIV assembly sites is unclear. We determined that tetherin is significantly upregulated upon macrophage infection and localizes to an intracellular virus-containing compartment (VCC). Tetherin localized at the virus-VCC membrane interface, suggesting that tetherin physically tethers virions in VCCs. Tetherin knockdown diminished and redistributed VCCs within macrophages and promoted HIV release and cell-cell transmission. The HIV Vpu protein, which downregulates tetherin from the plasma membrane, did not fully overcome tetherin-mediated restriction of particle release in macrophages. Thus, tetherin is essential for VCC formation, and may account for morphologic differences in the apparent HIV assembly sites in macrophages versus T cells.