Lymphocytes from HIV-infected individuals show aberrant inositol polyphosphate metabolism which reverses after zidovudine therapy.
Lymphocytes or lymphoblastoid cells that have been infected by HIV in vitro or exposed to its envelope glycoprotein (gp120) show abnormal inositol polyphosphate-mediated signal transduction and associated defects in calcium regulation. Such cells behave as though they were chronically activated and fail to respond to further activating signals. We now show that similar changes are seen in lymphocytes obtained from HIV-infected subjects at various stages of infection, despite the fact that only a minority of such cells are infected. Furthermore, the defect in the phosphatidylinositol hydrolysis pathway in lymphocytes obtained from AIDS patients reverses after treatment with zidovudine, in parallel with improvements in phytohaemagglutinin-induced proliferative response and interferon-gamma production.
Department of Immunology, St Mary's Hospital Medical School, London, UK.
K E
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Nye
K A
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Knox
A J
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Pinching
D000163:Acquired Immunodeficiency Syndrome / Q000097:blood* / Q000188:drug therapy; D015496:CD4-Positive T-Lymphocytes; D002118:Calcium / Q000378:metabolism; D015658:HIV Infections / Q000097:blood* / Q000188:drug therapy; D006801:Humans; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism; D007295:Inositol Phosphates / Q000378:metabolism*; D007371:Interferon-gamma / Q000378:metabolism; D007958:Leukocyte Count; D008213:Lymphocyte Activation / Q000187:drug effects; D008214:Lymphocytes / Q000187:drug effects / Q000378:metabolism*; D010716:Phosphatidylinositols / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory; D015215:Zidovudine / Q000627:therapeutic use*
D007295:Inositol Phosphates; D010716:Phosphatidylinositols; D015215:Zidovudine; D007371:Interferon-gamma; D015544:Inositol 1,4,5-Trisphosphate; D002118:Calcium