title: CD4-independent infection by HIV-2 is mediated by fusin/CXCR4.
abstract: Several members of the chemokine receptor family have been shown to function in association with CD4 to permit HIV-1 entry and infection. However, the mechanism by which these molecules serve as CD4-associated cofactors is unclear. In the present report, we show that one member of this family, termed Fusin/ CXCR4, is able to function as an alternative receptor for some isolates of HIV-2 in the absence of CD4. This conclusion is supported by the finding that (1) CD4-independent infection by these viruses is inhibited by an anti-Fusin monoclonal antibody, (2) Fusin expression renders human and nonhuman CD4-negative cell lines sensitive to HIV-2-induced syncytium induction and/or infection, and (3) Fusin is selectively down-regulated from the cell surface following HIV-2 infection. The finding that one chemokine receptor can function as a primary viral receptor strongly suggests that the HIV envelope glycoprotein contains a binding site for these proteins and that differences in the affinity and/or the availability of this site can extend the host range of these viruses to include a number of CD4-negative cell types.
authors.affiliation: Hematology-Oncology Division, University of Pennsylvania, Philadelphia 19104, USA.
authors.forename: M J
authors.initials: MJ
authors.lastname: Endres
authors.forename: P R
authors.initials: PR
authors.lastname: Clapham
authors.forename: M
authors.initials: M
authors.lastname: Marsh
authors.forename: M
authors.initials: M
authors.lastname: Ahuja
authors.forename: J D
authors.initials: JD
authors.lastname: Turner
authors.forename: A
authors.initials: A
authors.lastname: McKnight
authors.forename: J F
authors.initials: JF
authors.lastname: Thomas
authors.forename: B
authors.initials: B
authors.lastname: Stoebenau-Haggarty
authors.forename: S
authors.initials: S
authors.lastname: Choe
authors.forename: P J
authors.initials: PJ
authors.lastname: Vance
authors.forename: T N
authors.initials: TN
authors.lastname: Wells
authors.forename: C A
authors.initials: CA
authors.lastname: Power
authors.forename: S S
authors.initials: SS
authors.lastname: Sutterwala
authors.forename: R W
authors.initials: RW
authors.lastname: Doms
authors.forename: N R
authors.initials: NR
authors.lastname: Landau
authors.forename: J A
authors.initials: JA
authors.lastname: Hoxie
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D001402:B-Lymphocytes / Q000821:virology; D001483:Base Sequence; D015704:CD4 Antigens / Q000378:metabolism*; D016466:CHO Cells; D002459:Cell Fusion / Q000187:drug effects; D006224:Cricetinae; D015536:Down-Regulation; D014644:Genetic Variation; D015498:HIV-2 / Q000235:genetics / Q000254:growth & development*; D006801:Humans; D008214:Lymphocytes / Q000821:virology*; D008565:Membrane Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D008969:Molecular Sequence Data; D011784:Quail; D019718:Receptors, CXCR4; D015728:Receptors, HIV / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism; D013601:T-Lymphocytes / Q000821:virology
chemical_list: D000911:Antibodies, Monoclonal; D015704:CD4 Antigens; D008565:Membrane Proteins; D019718:Receptors, CXCR4; D015728:Receptors, HIV; D011994:Recombinant Proteins