title: Effects of changes in gp120-CD4 binding affinity on human immunodeficiency virus type 1 envelope glycoprotein function and soluble CD4 sensitivity.
abstract: Mutant gp120 glycoproteins exhibiting a range of affinities for CD4 were tested for ability to form syncytia and to complement an env-defective provirus for replication. Surprisingly, gp120 mutants that efficiently induced syncytia and/or complemented virus replication were identified that exhibited marked (up to 50-fold) reductions in CD4-binding ability. Temperature-dependent changes in gp120, which result in a seven- to ninefold increase in affinity for CD4, were shown not to be necessary for subsequent membrane fusion or virus entry events. Mutant glycoproteins demonstrating even relatively small decreases in CD4-binding ability exhibited reduced sensitivity to soluble CD4. The considerable range of CD4-binding affinities tolerated by replication-competent HIV-1 variants has important implications for antiviral strategies directed at the gp120-CD4 interaction.
authors.affiliation: Division of Human Retrovirology, Dana-Farber Cancer Institute, Boston, Massachusetts.
authors.forename: M
authors.initials: M
authors.lastname: Thali
authors.forename: U
authors.initials: U
authors.lastname: Olshevsky
authors.forename: C
authors.initials: C
authors.lastname: Furman
authors.forename: D
authors.initials: D
authors.lastname: Gabuzda
authors.forename: J
authors.initials: J
authors.lastname: Li
authors.forename: J
authors.initials: J
authors.lastname: Sodroski
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D015704:CD4 Antigens / Q000737:chemistry / Q000378:metabolism*; D002460:Cell Line; D002522:Chlorocebus aethiops; D015699:HIV Envelope Protein gp120 / Q000235:genetics / Q000378:metabolism*; D015497:HIV-1 / Q000502:physiology*; D008561:Membrane Fusion; D011485:Protein Binding; D011994:Recombinant Proteins / Q000378:metabolism; D012995:Solubility; D013329:Structure-Activity Relationship; D013696:Temperature; D014779:Virus Replication
chemical_list: D015704:CD4 Antigens; D015699:HIV Envelope Protein gp120; D011994:Recombinant Proteins