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.
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.
Tahara-Hanaoka
S
S
Department of Immunology, Institute of Basic Medical Sciences, University of Tsukuba, Ibaraki, Japan.
Ushijima
Y
Y
Tarui
H
H
Wada
M
M
Hara
T
T
Imanishi
S
S
Yamaguchi
T
T
Hattori
T
T
Nakauchi
H
H
Koito
A
A
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
D015704:CD4 Antigens; D015699:HIV Envelope Protein gp120; D008934:Mitogens; D019718:Receptors, CXCR4; D011993:Recombinant Fusion Proteins; D013755:Tetradecanoylphorbol Acetate