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Liposomes, Exosomes, and Virosomes: From Modeling Complex
Membrane Processes to Medical Diagnostics and Drug Delivery
Poster Abstracts
115
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.