Electron tomography visualization of HIV-1 fusion with target cells using inhibitors to trap the prehairpin intermediate
- California Institute of Technology, United States
- University of Utah School of Medicine, United States
Abstract
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.
Data availability
Raw datasets are freely available upon request. Interested parties should contact ladinsky@caltech.edu, and we will place requested datasets onto an externally accessible Caltech Box Server. Requestors will then be provided with a direct URL link from which they can download the files at their convenience.
Article and author information
Author details
Funding
National Institute of General Medical Sciences (2 P50 AI150464)
- Michael S Kay
- Pamela J Bjorkman
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Copyright
© 2020, Ladinsky et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Electron tomography visualization of HIV-1 fusion with target cells using inhibitors to trap the prehairpin intermediate
eLife 9:e58411.
https://doi.org/10.7554/eLife.58411
