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

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.

journal_name

Nat Chem Biol

journal_title

Nature chemical biology

authors

Yang ST,Kiessling V,Simmons JA,White JM,Tamm LK

doi

10.1038/nchembio.1800

subject

Has Abstract

pub_date

2015-06-01 00:00:00

pages

424-31

issue

6

eissn

1552-4450

issn

1552-4469

pii

nchembio.1800

journal_volume

11

pub_type

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