title: Adaptation of a CCR5-using, primary human immunodeficiency virus type 1 isolate for CD4-independent replication.
abstract: The gp120 envelope glycoprotein of the human immunodeficiency virus type 1 (HIV-1) promotes virus entry by sequentially binding CD4 and chemokine receptors on the target cell. Primary, clinical HIV-1 isolates require interaction with CD4 to allow gp120 to bind the CCR5 chemokine receptor efficiently. We adapted a primary HIV-1 isolate, ADA, to replicate in CD4-negative canine cells expressing human CCR5. The gp120 changes responsible for the adaptation were limited to alteration of glycosylation addition sites in the V2 loop-V1-V2 stem. The gp120 glycoproteins of the adapted viruses bound CCR5 directly, without prior interaction with CD4. Thus, a major function of CD4 binding in the entry of primary HIV-1 isolates can be bypassed by changes in the gp120 V1-V2 elements, which allow the envelope glycoproteins to assume a conformation competent for CCR5 binding.
authors.affiliation: Department of Cancer, Dana-Farber Cancer Institute, Children's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA.
authors.forename: P
authors.initials: P
authors.lastname: Kolchinsky
authors.forename: T
authors.initials: T
authors.lastname: Mirzabekov
authors.forename: M
authors.initials: M
authors.lastname: Farzan
authors.forename: E
authors.initials: E
authors.lastname: Kiprilov
authors.forename: M
authors.initials: M
authors.lastname: Cayabyab
authors.forename: L J
authors.initials: LJ
authors.lastname: Mooney
authors.forename: H
authors.initials: H
authors.lastname: Choe
authors.forename: J
authors.initials: J
authors.lastname: Sodroski
mesh_terms: D000818:Animals; D015704:CD4 Antigens / Q000502:physiology*; D004285:Dogs; D015699:HIV Envelope Protein gp120 / Q000502:physiology; D015497:HIV-1 / Q000502:physiology*; D006367:HeLa Cells; D006801:Humans; D019713:Receptors, CCR5 / Q000502:physiology*; D014779:Virus Replication
chemical_list: D015704:CD4 Antigens; D015699:HIV Envelope Protein gp120; D019713:Receptors, CCR5