title: A seven-transmembrane domain receptor involved in fusion and entry of T-cell-tropic human immunodeficiency virus type 1 strains.
abstract: Entry of human immunodeficiency virus type 1 (HIV-1) into cells requires binding to CD4 and fusion with a cellular membrane. Fusion does not occur in most nonhuman cells even when they express human CD4, indicating that one or more human accessory factors are required for virus infection. Recently, a seven-transmembrane domain protein has been shown to serve as an accessory factor for T-cell-tropic (T-tropic) HIV-1 isolates (Y. Feng, C. C. Broder, P. E. Kennedy, and E. A. Berger, Science 272:872-877, 1996). Here we show that expression of this glycoprotein, termed fusin, in murine, feline, simian, and quail cell lines, in conjunction with human CD4, rendered these cells fully permissive for HIV-1 envelope glycoprotein (Env)-mediated membrane fusion. Expression of CD4 or fusin alone did not permit fusion. In addition, introduction of fusin and CD4 into a human cell line, U87MG, that is resistant to HIV-1 induced syncytium formation and to infection by HIV-1 when expressing CD4 alone made this cell line permissive for Env-mediated cell-cell fusion. Fusion was observed only with T-tropic Env proteins. Macrophage-tropic (M-tropic) Env proteins from the SF162, ADA, and Ba-L HIV-1 strains did not fuse with cells expressing fusin and CD4, suggesting that M-tropic viruses utilize an accessory molecule other than fusin. Finally, coexpression of fusin and CD4 made both a murine and feline cell line susceptible to virus infection by T-tropic, but not M-tropic, HIV-1 strains.
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia 19104, USA.
authors.forename: J F
authors.initials: JF
authors.lastname: Berson
authors.forename: D
authors.initials: D
authors.lastname: Long
authors.forename: B J
authors.initials: BJ
authors.lastname: Doranz
authors.forename: J
authors.initials: J
authors.lastname: Rucker
authors.forename: F R
authors.initials: FR
authors.lastname: Jirik
authors.forename: R W
authors.initials: RW
authors.lastname: Doms
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D015703:Antigens, CD / Q000502:physiology; D001254:Astrocytoma; D001483:Base Sequence; D015704:CD4 Antigens / Q000502:physiology*; D002415:Cats; D002460:Cell Line; D002462:Cell Membrane / Q000502:physiology / Q000648:ultrastructure; D003001:Cloning, Molecular; D003370:Coturnix; D017931:DNA Primers; D005333:Fetus; D015723:Gene Library; D015686:Gene Products, env / Q000502:physiology; D015726:Giant Cells; D015497:HIV-1 / Q000276:immunology / Q000502:physiology*; D006367:HeLa Cells; D006801:Humans; D008565:Membrane Proteins / Q000096:biosynthesis / Q000737:chemistry / Q000502:physiology*; D051379:Mice; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D017433:Protein Structure, Secondary; D019718:Receptors, CXCR4; D015728:Receptors, HIV / Q000502:physiology*; D013154:Spleen; D013601:T-Lymphocytes / Q000276:immunology* / Q000821:virology*; D014407:Tumor Cells, Cultured
chemical_list: D015703:Antigens, CD; D015704:CD4 Antigens; D017931:DNA Primers; D015686:Gene Products, env; D008565:Membrane Proteins; D019718:Receptors, CXCR4; D015728:Receptors, HIV