6th International AIDS Conference


San Francisco, California, USA — June 20-23, 1990

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Is the observed abnormality in the inositol polyphosphate pathway in HIV infected cells a general phenomenon in viral infection?

Int Conf AIDS 1990 Jun 20-23; 6:323 (abstract no. 1039)
Nye KE, Pinching AJ; Department of Immunology, St. Mary's Hospital Medical School, London, UK

OBJECTIVE: To isolate that part(s) of the phosphatidyl inositol hydrolysis pathway responsible for the aberrant metabolism of inositol polyphosphates observed in HIV infected cells (Nye & Pinching AIDS 4 (1); 41 - 45 1990).

METHOD: Cells, either lymphocytes separated from HIV infected subjects or taken from H9 or Hep2 lines infected with HIV or Respiratory Syncytial Virus (RSV) respectively, were lysed by freeze-fracture and incubated with 2uCi of D-myo-[2-3H] inositol 1,3,4,5-tetrakisphosphate (InsP4) [1Ci/mmol] for 15 min at 37 degrees C in the presence of 2mM ATP, 4mM Mg2+ and 2mM 2,3-bisphosphodiglycerate at pH 8.0. Activity was terminated with perchloric acid, neutralised and the inositol polyphosphate profile determined on HPLC using a Partisil-SAX ion exchange column and a water to formate gradient.

RESULTS: In normal control lymphocytes and uninfected H9 and Hep2 cells, InsP4 was rapidly converted to inositol while in the virally infected cells, either HIV or RSV, InsP4 remained unchanged.

CONCLUSION: Infection with either of these RNA viruses causes the same observable abnormality, suggesting that this is an effect common to viral integration. The observations in addition imply that the Ins(1,4,5)P3/Ins(1,3,4,5)P4-5-phosphatase is either down regulated or defective. These preliminary results are being extended in our laboratory to include DNA viruses and to examine more closely the 5-phosphatase defect.

Keywords: AEGIS, Inositol, Polyphosphates, Phosphoric Monoester Hydrolases, Phosphatidylinositols, Cells, Adenosine Triphosphate, Chromatography, High Pressure Liquid, Hydrolysis, Subcellular Fractions, Sarcoplasmic Reticulum, abnormalities, ICA6KWDaegis,inositol,polyphosphates,phosphoricmonoesterhydrolases,phosphatidylinositols,cells,adenosinetriphosphate,chromatography,highpressureliquid,hydrolysis,subcellularfractions,sarcoplasmicreticulum,abnormalities,ica6

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