Trans-activation of HIV-1 LTR-directed gene expression by tat requires protein kinase C

EMBO J. 1990 Apr;9(4):1165-70. doi: 10.1002/j.1460-2075.1990.tb08223.x.

Abstract

Human immunodeficiency virus (HIV) spends a significant part of the viral life cycle as a latent provirus integrated into the host genome. Activation of latent HIV-1 requires mitogenic stimulation of the cell, which increases basal viral transcription, and the HIV-1 tat protein. As tat itself dramatically increases HIV-1 gene expression, it too is presumably regulated in the latent state, and may also be activated by mitogenic stimulation. We show here that depletion of protein kinase C (PKC), which is essential to the stimulation of T cells by several mitogens, dramatically reduces HIV-1 transactivation without affecting synthesis of tat protein. Transactivation in PKC-depleted cells can be restored by transfection with a PKC expression vector. The requirement for PKC in trans-activation does not involve the PMA-responsive enhancer elements responsible for the effect of mitogens on basal transcription. Our results indicate that PKC regulates the process of HIV-1 transactivation, suggesting a key role for the mitogenic induction of trans-activation in the transition of HIV from latency to productive growth.

MeSH terms

  • Cell Line
  • Gene Expression Regulation, Viral*
  • Gene Products, tat / metabolism*
  • Genes, Viral*
  • HIV-1 / genetics*
  • Humans
  • Mutation
  • Phorbol 12,13-Dibutyrate / metabolism
  • Plasmids
  • Promoter Regions, Genetic
  • Protein Kinase C / deficiency
  • Protein Kinase C / genetics
  • Protein Kinase C / metabolism*
  • Repetitive Sequences, Nucleic Acid*
  • Trans-Activators / metabolism*
  • Transcriptional Activation*
  • Transfection
  • tat Gene Products, Human Immunodeficiency Virus

Substances

  • Gene Products, tat
  • Trans-Activators
  • tat Gene Products, Human Immunodeficiency Virus
  • Phorbol 12,13-Dibutyrate
  • Protein Kinase C