Alteration of DNA topoisomerase II activity during infection of H9 cells by human immunodeficiency virus type 1 in vitro: a target for potential therapeutic agents.
Infection of H9 cells with human immunodeficiency virus type 1 (HIV-1) was found to decrease the phosphorylation of DNA topoisomerase II during the initial phase of infection. Simultaneously, with a later overshoot of phosphorylation and the subsequent activation of DNA topoisomerase II, the production of HIV-1 started. Applying three new protein kinase C inhibitors from the class of O-alkylglycerophospholipids we demonstrated that inhibition of protein kinase C-mediated phosphorylation of DNA topoisomerase II resulted in an inhibition of HIV-1 production. Based on the differential effect of the two protein kinase C activators, phorbol ester and bryostatin, we conclude that phosphorylation of DNA topoisomerase II is mediated by the form alpha and gamma of protein kinase C. These data suggest that agents which inhibit these two forms of protein kinase C are also potential candidates for an anti-HIV therapy.
Matthes
E
E
Zentralinstitut für Molekularbiologie, Akademie der Wissenschaften der D.D.R., G.D.R.
Langen
P
P
Brachwitz
H
H
Schröder
H C
HC
Maidhof
A
A
Weiler
B E
BE
Renneisen
K
K
Müller
W E
WE
D000818:Animals; D054713:Bryostatins; D002460:Cell Line; D004264:DNA Topoisomerases, Type I / Q000378:metabolism*; D004591:Electrophoresis, Polyacrylamide Gel; D015497:HIV-1 / Q000187:drug effects / Q000254:growth & development*; D066298:In Vitro Techniques; D007783:Lactones / Q000494:pharmacology; D008244:Lysophosphatidylcholines / Q000494:pharmacology; D018942:Macrolides; D010766:Phosphorylation; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D013601:T-Lymphocytes / Q000201:enzymology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D054713:Bryostatins; D007783:Lactones; D008244:Lysophosphatidylcholines; D018942:Macrolides; C065880:1-O-oleoyl-2-chloro-2-deoxy-3-phosphatidylcholine; C065881:1-O-oleoyl-3-chloro-3-deoxy-2-phosphatidylcholine; C065898:2-O-oleoyl-1-chloro-1-deoxy-3-phosphatidylcholine; C046785:bryostatin 1; D011493:Protein Kinase C; D004264:DNA Topoisomerases, Type I; D013755:Tetradecanoylphorbol Acetate