title: Inhibition of human immunodeficiency virus fusion by a monoclonal antibody to a coreceptor (CXCR4) is both cell type and virus strain dependent.
abstract: CXCR4 (also termed fusin, LESTR, or HUMSTR) is a member of the G-protein-coupled chemokine receptor family with seven membrane-spanning domains. CXCR4 acts as a coreceptor for syncytium-inducing human immunodeficiency virus type 1 (HIV-1) strains, conferring entry into CD4+ cells. We show here that a novel mouse monoclonal antibody (12G5) that recognizes CXCR4 blocked cell-to-cell fusion and cell free-virus infection of CXCR4+ CD4+ RD rhabdomyosarcoma cells by seven HIV-1 and HIV-2 strains that had various cell tropisms for different CD4+ human cell types. Yet the majority of the members of the same virus panel resisted 12G5 inhibition on T-cell lines. When inhibition was observed on these cell types, it was both cell type and virus strain dependent. In at least one situation, 12G5 failed to block LAI infection of cells expressing CXCR4 as the only available coreceptor. Our observations suggest that CXCR4 could be processed or presented differently depending on the cell type, allowing some strains to evade 12G5 inhibition. Alternatively, since several of the viruses could infect certain CXCR4- CD4+ cell lines, it is conceivable that alternative coreceptors are active, enabling individual HIV strains to choose between compatible coreceptors during entry into cells. Moreover, the strain dependency of 12G5 inhibition implies that the interaction of different HIVs with CXCR4 varies.
authors.affiliation: Virology Laboratory, Chester Beatty Laboratories, The Institute of Cancer Research, London, United Kingdom.
authors.forename: A
authors.initials: A
authors.lastname: McKnight
authors.forename: D
authors.initials: D
authors.lastname: Wilkinson
authors.forename: G
authors.initials: G
authors.lastname: Simmons
authors.forename: S
authors.initials: S
authors.lastname: Talbot
authors.forename: L
authors.initials: L
authors.lastname: Picard
authors.forename: M
authors.initials: M
authors.lastname: Ahuja
authors.forename: M
authors.initials: M
authors.lastname: Marsh
authors.forename: J A
authors.initials: JA
authors.lastname: Hoxie
authors.forename: P R
authors.initials: PR
authors.lastname: Clapham
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology*; D015704:CD4 Antigens; D002460:Cell Line; D015658:HIV Infections / Q000821:virology*; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D008565:Membrane Proteins / Q000276:immunology*; D051379:Mice; D009928:Organ Specificity; D019718:Receptors, CXCR4; D015728:Receptors, HIV / Q000276:immunology*; D014779:Virus Replication / Q000187:drug effects*
chemical_list: D000911:Antibodies, Monoclonal; D015704:CD4 Antigens; D008565:Membrane Proteins; D019718:Receptors, CXCR4; D015728:Receptors, HIV