HIV gp41-mediated membrane fusion occurs at edges of cholesterol-rich lipid domains.
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.
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.
Sung-Tae
ST
Yang
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.
Volker
V
Kiessling
1] Center for Membrane Biology, University of Virginia, Charlottesville, Virginia, USA. [2] Department of Cell Biology, University of Virginia, Charlottesville, Virginia, USA.
James A
JA
Simmons
1] Center for Membrane Biology, University of Virginia, Charlottesville, Virginia, USA. [2] Department of Cell Biology, University of Virginia, Charlottesville, Virginia, USA.
Judith M
JM
White
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.
Lukas K
LK
Tamm
D002462:Cell Membrane / Q000378:metabolism*; D002784:Cholesterol / Q000378:metabolism*; D057809:HEK293 Cells; D006678:HIV / Q000502:physiology; D015700:HIV Envelope Protein gp41 / Q000378:metabolism*; D006801:Humans; D008051:Lipid Bilayers / Q000378:metabolism; D008561:Membrane Fusion; D021962:Membrane Microdomains / Q000378:metabolism*; D008856:Microscopy, Fluorescence; D008954:Models, Biological; D013601:T-Lymphocytes / Q000378:metabolism; D053835:Unilamellar Liposomes; D014771:Virion / Q000502:physiology
D015700:HIV Envelope Protein gp41; D008051:Lipid Bilayers; D053835:Unilamellar Liposomes; D002784:Cholesterol