title: The molecular basis of HIV entry.
abstract: Infection by HIV starts when the virus attaches to a susceptible cell. For viral replication to continue, the viral envelope must fuse with a cellular membrane, thereby delivering the viral core to the cytoplasm, where the RNA genome is reverse-transcribed. The key players in this entry by fusion are the envelope glycoprotein, on the viral side, and CD4 and a co-receptor, CCR5 or CXCR4, on the cellular side. Here, the interplay of these molecules is reviewed from cell-biological, structural, mechanistic, and modelling-based perspectives. Hypotheses are evaluated regarding the cellular compartment for entry, the transfer of virus through direct cell-to-cell contact, the sequence of molecular events, and the number of molecules involved on each side of the virus-cell divide. An emerging theme is the heterogeneity among the entry mediators on both sides, a diversity that affects the efficacy of entry inhibitors, be they small-molecule ligands, peptides or neutralizing antibodies. These insights inform rational strategies for therapy as well as vaccination.
authors.affiliation: Department of Microbiology and Immunology, Cornell University, Weill Cornell Medical College, 1300 York Avenue, Box 62, New York, NY 10065-4896, USA. pek2003@med.cornell.edu
authors.forename: Per Johan
authors.initials: PJ
authors.lastname: Klasse
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000821:virology; D006678:HIV / Q000502:physiology*; D015658:HIV Infections / Q000635:transmission / Q000821:virology*; D054884:Host-Pathogen Interactions; D054298:Human Immunodeficiency Virus Proteins / Q000502:physiology; D006801:Humans; D008561:Membrane Fusion; D014771:Virion / Q000502:physiology; D053585:Virus Attachment; D053586:Virus Internalization
chemical_list: D054298:Human Immunodeficiency Virus Proteins