HIV virions sense plasma membrane heterogeneity for cell entry
Year: 2017
Journal: Sci. Adv., Volume 3, JUN
Authors: Yang, Sung-Tae; Kreutzberger, Alex J. B.; Kiessling, Volker; Ganser-Pornillos, Barbie K.; White, Judith M.; Tamm, Lukas K.
Organizations: NIH [R01 AI30557, R21 AI103601]
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.
