title: The HIV Env-mediated fusion reaction.
abstract: The current general model of HIV viral entry involves the binding of the trimeric viral envelope glycoprotein gp120/gp41 to cell surface receptor CD4 and chemokine co-receptor CXCR4 or CCR5, which triggers conformational changes in the envelope proteins. Gp120 then dissociates from gp41, allowing for the fusion peptide to be inserted into the target membrane and the pre-hairpin configuration of the ectodomain to form. The C-terminal heptad repeat region and the leucine/isoleucine zipper region then form the thermostable six-helix coiled-coil, which drives the membrane merger and eventual fusion. This model needs updating, as there has been a wealth of data produced in the last few years concerning HIV entry, including target cell dependencies, fusion kinetic data, and conformational intermediates. A more complete model must include the involvement of membrane microdomains, actin polymerization, glycosphingolipids, and possibly CD4 and chemokine signaling in entry. In addition, kinetic experiments involving the addition of fusion inhibitors have revealed some of the rate-limiting steps in this process, adding a temporal component to the model. A review of these data that may require an updated version of the original model is presented here.
authors.affiliation: Laboratory of Experimental and Computational Biology, Center for Cancer Research, NCI-Frederick, National Institute of Health, Miller Drive, Frederick, MD 21702-1201, USA.
authors.forename: Stephen A
authors.initials: SA
authors.lastname: Gallo
authors.forename: Catherine M
authors.initials: CM
authors.lastname: Finnegan
authors.forename: Mathias
authors.initials: M
authors.lastname: Viard
authors.forename: Yossef
authors.initials: Y
authors.lastname: Raviv
authors.forename: Antony
authors.initials: A
authors.lastname: Dimitrov
authors.forename: Satinder S
authors.initials: SS
authors.lastname: Rawat
authors.forename: Anu
authors.initials: A
authors.lastname: Puri
authors.forename: Stewart
authors.initials: S
authors.lastname: Durell
authors.forename: Robert
authors.initials: R
authors.lastname: Blumenthal
mesh_terms: D015699:HIV Envelope Protein gp120 / Q000737:chemistry* / Q000378:metabolism; D015700:HIV Envelope Protein gp41 / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D007700:Kinetics; D008561:Membrane Fusion; D008958:Models, Molecular; D011487:Protein Conformation; D015728:Receptors, HIV / Q000378:metabolism
chemical_list: D015699:HIV Envelope Protein gp120; D015700:HIV Envelope Protein gp41; D015728:Receptors, HIV