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The function of coreceptor as a basis for the kinetic dissection of HIV type 1 envelope protein‐mediated cell fusion
Author(s) -
Chien MiaoPing,
Jiang Shibo,
Change DingKwo
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.07-9576com
Subject(s) - ectodomain , gp41 , lipid bilayer fusion , biophysics , chemistry , fusion , viral envelope , microbiology and biotechnology , glycoprotein , förster resonance energy transfer , viral entry , cell fusion , membrane , virology , biology , cell , receptor , virus , fluorescence , viral replication , biochemistry , genetics , physics , linguistics , philosophy , quantum mechanics , epitope , antigen
The function of HIV‐1 HXB2 envelope (Env) glycoprotein (gp) was investigated by surface plasmon resonance and fluorescence imaging techniques. Strikingly, it was found that gp120 shedding requires the presence of the X4 coreceptor. A similar coreceptor requirement was observed for the membrane mixing and the Env recruitment on the cell surface. However, exposure and membrane penetration of the fusion peptide do not require X4 and occur within the first minute after incubation of Env with CD4 and/or X4. Analogously X4 was not required but enhanced binding of the fusion inhibitor. In contrast, bundle formation of the gp41 ectodomain, as monitored by NC‐1, was accelerated by the presence of X4. The kinetics of these key post‐Env binding events as determined in real time by fluorescence microscopic imaging, coupled with the differential coreceptor requirement, led to the proposition that gp120 shedding, which takes place from 1 to 10 min after engagement of receptor and coreceptor to Env, is a primary function of the coreceptor. The shedding of the surface subunits is needed for the subsequent processes including hemi‐fusion, full fusion, and Env recruitment. The temporal order of these fusogenic steps allows construction of a refined model on the Env‐mediated cell fusion event. Chien M.‐P., Jiang, S., Chang D.‐K. The function of coreceptor as a basis for the kinetic dissection of HIV type 1 Env‐mediated cell fusion. FASEB J. 22, 1179–1192 (2008)