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Nat Chem Biol. 2015 Jun;11(6):424-31. doi: 10.1038/nchembio.1800. Epub 2015 Apr 27.

HIV gp41-mediated membrane fusion occurs at edges of cholesterol-rich lipid domains.

Author information

1
1] Department of Molecular Physiology and Biological Physics, University of Virginia, Charlottesville, Virginia, USA. [2] Center for Membrane Biology, University of Virginia, Charlottesville, Virginia, USA.
2
1] Center for Membrane Biology, University of Virginia, Charlottesville, Virginia, USA. [2] Department of Cell Biology, University of Virginia, Charlottesville, Virginia, USA.

Abstract

Lipid rafts in plasma membranes have emerged as possible platforms for the entry of HIV and other viruses into cells. However, little is known about how lipid phase heterogeneity contributes to viral entry because of the fine-grained and still poorly understood complexity of biological membranes. We used model systems mimicking HIV envelopes and T cell membranes and found that raft-like liquid-ordered (Lo-phase) lipid domains were necessary and sufficient for efficient membrane targeting and fusion. Interestingly, membrane binding and fusion were low in homogeneous liquid-disordered (Ld-phase) and Lo-phase membranes, indicating that lipid phase heterogeneity is essential. The HIV fusion peptide preferentially targeted to Lo-Ld boundary regions and promoted full fusion at the interface between ordered and disordered lipids. Ld-phase vesicles proceeded only to hemifusion. Thus, we propose that edges but not areas of raft-like ordered lipid domains are vital for HIV entry and membrane fusion.

Comment in

PMID:
25915200
PMCID:
PMC4433777
DOI:
10.1038/nchembio.1800
[Indexed for MEDLINE]
Free PMC Article

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