title: Differential level in co-down-modulation of CD4 and CXCR4 primed by HIV-1 gp120 in response to phorbol ester, PMA, among HIV-1 isolates.
abstract: HIV-1 enters cells through interacting with cell surface molecules such as CD4 and chemokine receptors. We generated recombinant soluble gp120s derived from T-cell line-tropic (T-tropic) and macrophage-tropic (M-tropic) HIV-1 strains using a baculovirus expression system and investigated the association of CD4-gp120 complex with the chemokine receptor and/or other surface molecule(s). For monitoring the co-down-modulations of the CD4-gp120 complex, a cytoplasmic domain deletion mutant (tailless CD4), which is not capable of undergoing down-modulation by itself in response to phorbol ester PMA, was used. Our studies revealed both cell-type and HIV-1 strain-specific differences. We found that T-tropic gp120s were capable of priming co-down-modulation with tailless CD4 by interacting with CXCR4, whereas M-tropic SF162 gp120 could not after PMA treatment even in the presence of CCR5. Among the T-tropic HIV-1 envelopes, IIIB gp120 was the most potent. Furthermore, the ability of gp120 to prime the PMA induced co-down-modulation of tailless CD4 appeared to be dependent on the concentration of the principal coreceptor CXCR4. Nevertheless, the observation that IIIB gp120 strongly primed tailless CD4 co-down-modulation on human osteosarcoma HOS cells that express undetectable levels of surface CXCR4 raised the possibility that membrane component(s) other than those recently identified can be involved in down-modulation of the CD4/gp120 complexes.
authors.affiliation: Department of Immunology, Institute of Basic Medical Sciences, University of Tsukuba, Ibaraki, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Tahara-Hanaoka
authors.forename: Y
authors.initials: Y
authors.lastname: Ushijima
authors.forename: H
authors.initials: H
authors.lastname: Tarui
authors.forename: M
authors.initials: M
authors.lastname: Wada
authors.forename: T
authors.initials: T
authors.lastname: Hara
authors.forename: S
authors.initials: S
authors.lastname: Imanishi
authors.forename: T
authors.initials: T
authors.lastname: Yamaguchi
authors.forename: T
authors.initials: T
authors.lastname: Hattori
authors.forename: H
authors.initials: H
authors.lastname: Nakauchi
authors.forename: A
authors.initials: A
authors.lastname: Koito
mesh_terms: D016475:3T3 Cells; D000818:Animals; D016367:Baculoviridae; D015704:CD4 Antigens / Q000235:genetics / Q000378:metabolism*; D019556:COS Cells; D002462:Cell Membrane / Q000378:metabolism; D015536:Down-Regulation; D005822:Genetic Vectors; D015699:HIV Envelope Protein gp120 / Q000235:genetics / Q000378:metabolism*; D015497:HIV-1 / Q000302:isolation & purification / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D007739:L Cells; D051379:Mice; D008934:Mitogens; D011485:Protein Binding; D019718:Receptors, CXCR4 / Q000235:genetics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate
chemical_list: D015704:CD4 Antigens; D015699:HIV Envelope Protein gp120; D008934:Mitogens; D019718:Receptors, CXCR4; D011993:Recombinant Fusion Proteins; D013755:Tetradecanoylphorbol Acetate