Antireplicative and anticytopathic activities of prostratin, a non-tumor-promoting phorbol ester, against human immunodeficiency virus (HIV)

Prostratin, a non-tumor-promoting phorbol ester, inhibited human immunodeficiency virus (HIV)-induced cell killing and viral replication in a variety of acutely-infected cell systems. The potency and degree of cytoprotection was dependent on both viral strain and host cell type. Prostratin activated...

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Bibliographic Details
Published in:Antiviral research 1997, Vol.33 (2), p.87-97
Main Authors: Gulakowski, Robert J, McMahon, James B, Buckheit, Robert W, Gustafson, Kirk R, Boyd, Michael R
Format: Article
Language:English
Subjects:
Anti-HIV
Anti-HIV Agents - pharmacology
Antibiotics. Antiinfectious agents. Antiparasitic agents
Antiviral agents
Biological and medical sciences
Bryostatins
CD4 Antigens - metabolism
Cell Line
Cell Line, Transformed
Cytopathogenic Effect, Viral - drug effects
Down-Regulation
HIV-1 - drug effects
HIV-1 - physiology
Humans
Lactones - pharmacology
Macrolides
Medical sciences
Pharmacology. Drug treatments
Phorbol
Phorbol Esters - pharmacology
Prostratin
Virus Replication - drug effects
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Summary:Prostratin, a non-tumor-promoting phorbol ester, inhibited human immunodeficiency virus (HIV)-induced cell killing and viral replication in a variety of acutely-infected cell systems. The potency and degree of cytoprotection was dependent on both viral strain and host cell type. Prostratin activated viral expression in two latently-infected cell lines, but had little or no effect on chronically-infected cell lines. Prostratin caused a dose-dependent, but reversible, decrease in CD4 expression in the CEM-SS and MT-2 cell lines. This down-regulation of CD4 was inhibited in a dose-dependent manner by the protein kinase C (PKC) antagonist, staurosporine. In addition, the cytoprotective and cytostatic effects of prostratin in CEM-SS cells acutely infected with HIV-1 RF were reversed by bryostatin-1, a PKC agonist. Prostratin had no effect on reverse transcriptase or HIV-1 protease, nor did it inhibit the binding of gp120 to CD4. We conclude that prostratin inhibits HIV cytopathicity and replication through mechanism(s) involving PKC enzyme(s).
ISSN:0166-3542
1872-9096
DOI:10.1016/S0166-3542(96)01004-2