HIV virions sense plasma membrane heterogeneity for cell entry

It has been proposed that cholesterol in host cell membranes plays a pivotal role for cell entry of HIV. However, it remains largely unknown why virions prefer cholesterol-rich heterogeneous membranes to uniformly fluid membranes for membrane fusion. Using giant plasma membrane vesicles containing c...

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Bibliographic Details
Published in:Science advances 2017-06, Vol.3 (6), p.e1700338-e1700338
Main Authors: Yang, Sung-Tae, Kreutzberger, Alex J B, Kiessling, Volker, Ganser-Pornillos, Barbie K, White, Judith M, Tamm, Lukas K
Format: Article
Language:English
Subjects:
Biochemistry
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Summary:It has been proposed that cholesterol in host cell membranes plays a pivotal role for cell entry of HIV. However, it remains largely unknown why virions prefer cholesterol-rich heterogeneous membranes to uniformly fluid membranes for membrane fusion. Using giant plasma membrane vesicles containing cholesterol-rich ordered and cholesterol-poor fluid lipid domains, we demonstrate that the HIV receptor CD4 is substantially sequestered into ordered domains, whereas the co-receptor CCR5 localizes preferentially at ordered/disordered domain boundaries. We also show that HIV does not fuse from within ordered regions of the plasma membrane but rather at their boundaries. Ordered/disordered lipid domain coexistence is not required for HIV attachment but is a prerequisite for successful fusion. We propose that HIV virions sense and exploit membrane discontinuities to gain entry into cells. This study provides surprising answers to the long-standing question about the roles of cholesterol and ordered lipid domains in cell entry of HIV and perhaps other enveloped viruses.
ISSN:2375-2548
2375-2548
DOI:10.1126/sciadv.1700338