title: Altering expression levels of human immunodeficiency virus type 1 gp120-gp41 affects efficiency but not kinetics of cell-cell fusion.
abstract: Human immunodeficiency virus (HIV) entry into a host cell requires the fusion of virus and cellular membranes that is driven by interaction of the viral envelope glycoproteins gp120 and gp41 (gp120/gp41) with CD4 and a coreceptor, typically either CXCR4 or CCR5. The stoichiometry of gp120/gp41:CD4:CCR5 necessary to initiate membrane fusion is not known. To allow an examination of early events in gp120/gp41-driven membrane fusion, we developed a novel real-time cell-cell fusion assay. Using this assay to study fusion kinetics, we found that altering the cell surface density of gp120/gp41 affected the maximal extent of fusion without dramatically altering fusion kinetics. Collectively, these observations are consistent with the view that gp120/gp41-driven membrane fusion requires the formation of a threshold number of fusion-active intercellular gp120/gp41:CD4:CCR5 complexes. Furthermore, the probability of reaching this threshold is governed, in part, by the surface density of gp120/gp41.
authors.affiliation: Department of Biological Chemistry, Merck Research Laboratories, West Point, Pennsylvania 19486, USA.
authors.forename: Janet E
authors.initials: JE
authors.lastname: Lineberger
authors.forename: Renee
authors.initials: R
authors.lastname: Danzeisen
authors.forename: Daria J
authors.initials: DJ
authors.lastname: Hazuda
authors.forename: Adam J
authors.initials: AJ
authors.lastname: Simon
authors.forename: Michael D
authors.initials: MD
authors.lastname: Miller
mesh_terms: D002460:Cell Line; D005455:Fluorescent Antibody Technique; D015699:HIV Envelope Protein gp120 / Q000378:metabolism*; D015700:HIV Envelope Protein gp41 / Q000378:metabolism*; D015497:HIV-1 / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D008561:Membrane Fusion; D013997:Time Factors; D014760:Viral Fusion Proteins / Q000378:metabolism*; D014779:Virus Replication
chemical_list: D015699:HIV Envelope Protein gp120; D015700:HIV Envelope Protein gp41; D014760:Viral Fusion Proteins