Electron tomography visualization of HIV-1 fusion with target cells using fusion inhibitors to trap the pre-hairpin intermediate

eLife

Michael S Kay¹  Pamela J Bjorkman²  Priyanthi NP Gnanapragasam²  Mark S Ladinsky²  Anthony P West²  Zhi Yang² 

[1] Department of Biochemistry, University of Utah School of Medicine, Salt Lake City, United States;Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, United States;

关键词: HIV-1;    prehairpin intermediate;    TZM-bl cell;    electron tomography;    viral fusion;   

DOI  :  10.7554/eLife.58411

来源: DOAJ

【 摘 要 】

Fusion of HIV-1 with the membrane of its target cell, an obligate first step in virus infectivity, is mediated by binding of the viral envelope (Env) spike protein to its receptors, CD4 and CCR5/CXCR4, on the cell surface. The process of viral fusion appears to be fast compared with viral egress and has not been visualized by EM. To capture fusion events, the process must be curtailed by trapping Env-receptor binding at an intermediate stage. We have used fusion inhibitors to trap HIV-1 virions attached to target cells by Envs in an extended pre-hairpin intermediate state. Electron tomography revealed HIV-1 virions bound to TZM-bl cells by 2–4 narrow spokes, with slightly more spokes present when evaluated with mutant virions that lacked the Env cytoplasmic tail. These results represent the first direct visualization of the hypothesized pre-hairpin intermediate of HIV-1 Env and improve our understanding of Env-mediated HIV-1 fusion and infection of host cells.

【 授权许可】

Unknown