A model system for regulation of chronic HIV-1 infection in peripheral B lymphocytes.
B-HIV1, an oligoclone of immortalized cells derived from human peripheral B lymphocytes infected in vitro with the TIIIB isolate of HIV-1, produces low levels of replication-competent HIV when propagated in 1% serum, but increases production > or = 5-fold after phorbol myristate acetate (PMA) exposure. Electron microscopy reveals budding of mature virions from the plasma membrane, without concentration in endocytotic spaces. The PMA effect is specific for protein kinase activation, occurring upon exposure of B-HIV1 to those congeners capable of upregulating calcium and phospholipid dependent protein kinase C and susceptible to inhibition by the protein kinase antagonists H-7 and staurosporine. Induction could also be effected by another viral activator, 5-azacytidine, which acts via an alternate mechanism, and blocked by high doses of interferon-alpha but not the anti-viral nucleoside analog zidovudine (AZT). B-HIV1 may provide a model system for study of the regulation of chronic HIV infection in cells of B lymphocyte lineage.
Laurence
J
J
Department of Medicine, Cornell University Medical Center, New York, New York 10021.
Grimison
B
B
Rodriguez-Alfageme
C
C
Astrin
S M
SM
D001374:Azacitidine / Q000494:pharmacology; D001402:B-Lymphocytes / Q000382:microbiology* / Q000648:ultrastructure; D001483:Base Sequence; D015415:Biomarkers / Q000032:analysis; D002999:Clone Cells; D004305:Dose-Response Relationship, Drug; D016325:HIV Long Terminal Repeat; D015497:HIV-1 / Q000187:drug effects / Q000254:growth & development* / Q000648:ultrastructure; D006801:Humans; D008969:Molecular Sequence Data; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D047428:Protein Kinase Inhibitors; D011533:Proviruses / Q000254:growth & development; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014775:Virus Activation; D014779:Virus Replication / Q000187:drug effects
D015415:Biomarkers; D047428:Protein Kinase Inhibitors; D011493:Protein Kinase C; D001374:Azacitidine; D013755:Tetradecanoylphorbol Acetate