Open AccessThe molecular basis of HIV entry
Author(s) -
Klasse Per Johan
Publication year - 2012
Publication title -
cellular microbiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.542
H-Index - 138
eISSN - 1462-5822
pISSN - 1462-5814
DOI - 10.1111/j.1462-5822.2012.01812.x
Subject(s) - biology , viral entry , viral envelope , virology , lipid bilayer fusion , microbiology and biotechnology , glycoprotein , cytoplasm , cell fusion , viral replication , virus , computational biology , cell , genetics
Summary 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 CD 4 and a co‐receptor, CCR 5 or CXCR 4, 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.