Biophysical Society Thematic Meeting | Ascona, Switzerland

Liposomes, Exosomes, and Virosomes: From Modeling Complex Membrane Processes to Medical Diagnostics and Drug Delivery

Poster Abstracts

63-POS Board 32 Fine-Tuning of HIV Entry Sites by Recognition of Cellular Receptors in Heterogenous Cell Membranes

Sung-Tae Yang , Volker Kiessling, Lukas K. Tamm. University of Virginia, Charlottesville, VA, USA.

Pathogens have evolved sophisticated strategies for the attachment to target cells to evade host immune responses and to establish infection. Lipid rafts of host cell membranes serve as ubiquitous entry sites; however, it remains largely unknown why pathogens, including HIV, seem to prefer nanoscopic ordered lipid domains over more disordered fluid membrane regions for infection. This study provides surprising answers to the long-standing question about the roles of lipid rafts in HIV entry using giant plasma membrane vesicles (GPMVs), which are phase-separated into large-scale liquid-ordered (Lo) and liquid-disordered (Ld) membrane domains. We show that HIV does not enter cells from within lipid rafts but rather at the boundaries between raft and non-raft regions of the plasma membrane. The HIV receptor CD4 is substantially sequestered into the Lo phase while the coreceptor CCR5 localizes preferentially in Lo/Ld interfaces on GPMVs, suggesting that HIV particles initially bind to lipid rafts and then move to their boundaries, which seem to be prone to HIV entry by constituting energetically favorable spots for cell entry by membrane fusion. Lo/Ld phase coexistence is not required during the HIV attachment stage, but recognition of a membrane phase boundary is a prerequisite for successful HIV membrane fusion. We propose that the coalescence of lipid rafts plays a key role in many vital cellular processes including adaptive immune responses to combat infectious pathogens and that HIV preferentially hijacks membrane phase boundaries to gain entry into the cells.

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