HIV-1 gp41 binding to human T- and B-lymphocytes and monocytes is modulated by phorbol myristate acetate (PMA).
HIV-1 gp41 independently of CD4 binds to human T cells, B cells and monocytic cells. Since PMA downmodulates CD4 (HIV receptor) expression and inhibits HIV-1 dependent syncytia formation, we wanted to examine whether PMA could affect gp41 binding protein expression on human cells. The strong binding of HIV-1 recombinant soluble gp41 (rsgp41; Env aa539-684) to monocytes (CD14+) and B-lymphocytes (CD19+) and B lymphoblastoid cells (Raji) could be clearly decreased by treating the cells with PMA for 48 h, while the weak binding to T lymphocytes was slightly increased by this treatment. The PMA inhibitory- and enhancing-effects could be avoided by pretreatment with staurosporine (protein kinase C inhibitor). The PMA treatment of Raji and U937 (monocytic) cells resulted in a 50-60% decrease of gp41 binding proteins (gp41bps) detectable in cell lysates of these cells in comparison with lysates of buffer-treated cells, while in the case of H9-cells PMA treatment resulted in an increase of available gp41bps by about 35% in comparison with buffer-treated H9. Staurosporine pre-treatment could prevent these effects of PMA. Further studies of rsgp41-eluates from these buffer-treated or PMA-treated cells demonstrated that PMA modulated mainly expression of rsgp41bps of 37, 45, 50 and 62 kDa. These results indicate that PMA exerts different effects on human T, B and monocytic cells. Production by and expression on cells of HIV-1 gp41bps appear to depend on protein kinase C, supporting that the four proteins on human cells may act as receptor proteins for HIV-1 gp41.
Chen
Y H
YH
Institute for Hygiene, University Innsbruck, Austria.
Christiansen
A
A
Dierich
M P
MP
D000328:Adult; D001402:B-Lymphocytes / Q000737:chemistry / Q000378:metabolism*; D002462:Cell Membrane / Q000737:chemistry / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005434:Flow Cytometry; D015700:HIV Envelope Protein gp41 / Q000378:metabolism*; D006801:Humans; D008565:Membrane Proteins / Q000737:chemistry / Q000378:metabolism; D008970:Molecular Weight; D009000:Monocytes / Q000737:chemistry / Q000378:metabolism*; D011485:Protein Binding; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D011956:Receptors, Cell Surface / Q000737:chemistry / Q000378:metabolism; D019311:Staurosporine / Q000494:pharmacology; D013601:T-Lymphocytes / Q000737:chemistry / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*
D004791:Enzyme Inhibitors; D015700:HIV Envelope Protein gp41; D008565:Membrane Proteins; D011956:Receptors, Cell Surface; D011493:Protein Kinase C; D019311:Staurosporine; D013755:Tetradecanoylphorbol Acetate