Expression of HIV-1 nef decreases basal phosphatidyl-inositol 3-kinase activity.
CEM lymphoid cells expressing high levels of HIV-1 nef protein displayed a significant decrease in basal phosphatidyl-inositol 3-kinase (P13-kinase) activity associated with immunoprecipitates with anti-p85 regulatory subunit. In contrast, chronically infected U937 monocytic cells displayed a significant increase in basal P13-kinase activity in cells infected with HIV-1 nef compared to those infected with isogenic HIV-1 nef+. These findings suggest that HIV-1-nef expression is accompanied by a decrease in basal intracellular phosphatidyl-inositol 3-kinase activity and suggest that P13-kinase could be important for HIV-1 replication. Moreover, wortmannin, a potent in-vitro phosphatidyl-inositol 3-kinase inhibitor, can inhibit HIV-1 replication in U937 chronically infected cells. Together these results suggest a correlation between P13-kinase activity and HIV-1 replication.
Garcia
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Groupe de développement cellulaire et unité d'immunologie virale, Institut Pasteur, Paris, France.
D000730:Androstadienes / Q000494:pharmacology; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D015754:Genes, nef / Q000235:genetics*; D016655:HIV Core Protein p24; D015497:HIV-1 / Q000235:genetics* / Q000502:physiology; D066298:In Vitro Techniques; D019869:Phosphatidylinositol 3-Kinases; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000037:antagonists & inhibitors / Q000378:metabolism*; D014779:Virus Replication / Q000187:drug effects; D000077191:Wortmannin
D000730:Androstadienes; D004791:Enzyme Inhibitors; D016655:HIV Core Protein p24; D019869:Phosphatidylinositol 3-Kinases; D017853:Phosphotransferases (Alcohol Group Acceptor); D000077191:Wortmannin