Phorbol ester-mediated induction of HIV-1 from a chronically infected promonocyte clone: blockade by protein kinase inhibitors and relationship to tat-directed trans-activation. Academic Article uri icon

Overview

abstract

  • Potent inhibitors of protein kinases C and A, including 1-(5 isoquinolinyl sulfonyl) 2-methyl piperazine (H7), staurosporine, and 2-aminopurine, depressed phorbol ester-induced HIV-1 virion production and HIV-specific transcripts by greater than 90% in chronically infected promonocytic cells. Suppression was dose-dependent and occurred at concentration that had little effect on cell growth. These effects appeared to be specific to activation of the PKC-diacylglycerol system. They did not alter IUdr-mediated induction of HIV. In addition, PMA enhancement of an HIV-LTR driven reporter gene was not blocked by H7 in the presence or absence of exogenous tat, at concentrations capable of inhibiting upregulation of virus at the cellular level. Insight into the biochemical mechanisms of these processes is critical to understanding interactions of HIV with the immune system, and may eventually uncover new therapeutic strategies.

publication date

  • January 15, 1990

Research

keywords

  • 2-Aminopurine
  • Adenine
  • Alkaloids
  • Gene Products, tat
  • HIV-1
  • Isoquinolines
  • Piperazines
  • Protein Kinase Inhibitors
  • Tetradecanoylphorbol Acetate
  • Trans-Activators
  • Transcriptional Activation
  • Virus Replication

Identity

Scopus Document Identifier

  • 0025129069

Digital Object Identifier (DOI)

  • 10.1016/0006-291x(90)91952-o

PubMed ID

  • 2405849

Additional Document Info

volume

  • 166

issue

  • 1