The defect seen in the phosphatidylinositol hydrolysis pathway in HIV-infected lymphocytes and lymphoblastoid cells is due to inhibition of the inositol 1,4,5-trisphosphate 1,3,4,5-tetrakisphosphate 5-phosphomonoesterase.
Lymphocytes infected in vivo with HIV or lymphoblastoid cells exposed in vitro to either HIV or its envelope glycoprotein (gp120) show a defect in inositol polyphosphate-mediated signal transduction together with an associated abnormality in intracellular calcium regulation. The defect in patients reverses after treatment with the anti-retroviral agent zidovudine (AZT). We present evidence that the defect is at the level of the Ins (1,3,4,5)P4 5-phosphomonoesterase (PME) in these cells and that, though elevation of the intracellular ATP level partially down-regulates the activity of this enzyme, such changes alone are unable to account for the complete inhibition seen in HIV-infected cells.
Nye
K E
KE
Department of Immunology, St Mary's Hospital Medical School, London, UK.
Riley
G A
GA
Pinching
A J
AJ
D000255:Adenosine Triphosphate / Q000494:pharmacology; D002118:Calcium / Q000494:pharmacology; D002851:Chromatography, High Pressure Liquid; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation / Q000187:drug effects; D006678:HIV / Q000378:metabolism*; D015699:HIV Envelope Protein gp120 / Q000276:immunology; D006801:Humans; D006868:Hydrolysis; D000072181:Inositol Polyphosphate 5-Phosphatases; D008214:Lymphocytes / Q000378:metabolism*; D010716:Phosphatidylinositols / Q000378:metabolism*; D010744:Phosphoric Monoester Hydrolases / Q000502:physiology*; D015398:Signal Transduction; D015215:Zidovudine / Q000494:pharmacology
D015699:HIV Envelope Protein gp120; D010716:Phosphatidylinositols; D015215:Zidovudine; D000255:Adenosine Triphosphate; D010744:Phosphoric Monoester Hydrolases; D000072181:Inositol Polyphosphate 5-Phosphatases; D002118:Calcium