HIV-1 enters T cells by interaction of its envelope glycoprotein gp120 with the receptors CD4 and CXCR4 or CCR5, followed by gp41-assisted fusion with the host-cell plasma membrane. In Nature Chemical Biology, Yang et al. show that viral fusion occurs at edges of cholesterol-rich lipid-raft domains. Liposomes containing the gp41 fusion peptide 'preferentially' associate with membranes at the boundaries between lipid phases and fuse their contents by coalescence with similar patches on the opposing host-cell membrane. These lipid-phase boundaries are thought to be more deformable and could lower the energetic barriers associated with membrane fusion and thereby facilitate entry of the virus into the host cytoplasm. In Virology, Mefford et al. report two polymorphisms in gp120 that increase viral trophism for macrophages, which express CCR5 but express less CD4 than T cells. Enhanced gp120-CCR5 interactions occur and might explain the increased infection of macrophage-rich tissues such as brain.

Nat. Chem. Biol. (27 April 2015) doi:10.1038/nchembio.1800 & Virology 481, 210–222 (2015)