title: Association between disruption of CD4 receptor dimerization and increased human immunodeficiency virus type 1 entry.
abstract: BACKGROUND
  Human immunodeficiency virus (HIV) enters target cells by a membrane fusion process that involves a series of sequential interactions between its envelope glycoproteins, the CD4 receptor and CXCR4/CCR5 coreceptors. CD4 molecules are expressed at the cell surface of lymphocytes and monocytes mainly as monomers, but basal levels of CD4 dimers are also present at the cell surface of these cells. Previous evidence indicates that the membrane distal and proximal extracellular domains of CD4, respectively D1 and D4, are involved in receptor dimerization.
  
  
  RESULTS
  Here, we have used A201 cell lines expressing two CD4 mutants, CD4-E91K, E92K (D1 mutant) and CD4-Q344E (D4 mutant), harboring dimerization defects to analyze the role of CD4 dimerization in HIV-1 entry. Using entry assays based on beta-lactamase-Vpr or luciferase reporter activities, as well as virus encoding envelope glycoproteins derived from primary or laboratory-adapted strains, we obtained evidence suggesting an association between disruption of CD4 dimerization and increased viral entry efficiency.
  
  
  CONCLUSIONS
  Taken together, our results suggest that monomeric forms of CD4 are preferentially used by HIV-1 to gain entry into target cells, thus implying that the dimer/monomer ratio at the cell surface of HIV-1 target cells may modulate the efficiency of HIV-1 entry.
authors.affiliation: Department of Microbiology and Immunology, Université de Montréal, Montreal, Quebec, Canada. rachel.bourgeois@umontreal.ca
authors.forename: Rachel
authors.initials: R
authors.lastname: Bourgeois
authors.forename: Johanne
authors.initials: J
authors.lastname: Mercier
authors.forename: Isabelle
authors.initials: I
authors.lastname: Paquette-Brooks
authors.forename: Eric A
authors.initials: EA
authors.lastname: Cohen
mesh_terms: D015704:CD4 Antigens / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D019281:Dimerization; D015497:HIV-1 / Q000378:metabolism / Q000472:pathogenicity*; D006801:Humans; D008561:Membrane Fusion; D009154:Mutation
chemical_list: D015704:CD4 Antigens