Inhibition of protein kinase C results in decreased expression of bovine leukemia virus

J Virol. 1992 Jul;66(7):4427-33. doi: 10.1128/JVI.66.7.4427-4433.1992.

Abstract

The in vitro expression of bovine leukemia virus (BLV) in short-term cultured bovine peripheral blood mononuclear cells (PBMC) is associated with increased spontaneous lymphocyte blastogenesis. The purpose of this study was to determine whether intracellular pathways responsible for antigen- or mitogen-induced lymphocyte blastogenesis were also responsible for induction of BLV expression. The protein kinase C (PKC) inhibitor 1-(5-isoquinolinylsulfonyl)-3-methylpiperazine dihydrochloride (3-methyl H7) decreased blastogenesis in a dose-dependent manner, as measured by [3H]thymidine incorporation, in unstimulated, lipopolysaccharide-stimulated and phorbol ester (PMA)-stimulated BLV-infected PBMC. Similarly, 3-methyl H7 decreased BLV expression, as measured by production of gp51 envelope antigen or p24gag antigen, in BLV-infected PBMC under the same conditions. Using an RNase protection assay, the inhibition of BLV expression by 3-methyl H7 was shown to be due to decreased transcriptional activity. The cyclic GMP-dependent protein kinase and cyclic AMP-dependent protein kinase inhibitor N-(2-guanidinoethyl)-5-isoquinolinesulfonamide (HA1004) did not inhibit either BLV expression or blastogenesis of BLV-infected bovine PBMC. Additional evidence for the PKC-dependent expression of BLV was obtained by using a persistently BLV-infected B-lymphocyte cell line, NBC-13. Activation of PKC by PMA in NBC-13 cells increased BLV expression. 3-methyl H7 decreased the PMA-induced expression of BLV in NBC-13 cells in a dose-dependent manner, whereas HA1004 did not inhibit this expression. These results identify a mechanism for the induction of BLV expression through PKC activation and therefore indicate that latency and replication of BLV is controlled by normal B-lymphocyte intracellular signaling pathways.

MeSH terms

  • Animals
  • B-Lymphocytes / enzymology
  • B-Lymphocytes / microbiology
  • Cattle
  • Cattle Diseases / microbiology
  • Cells, Cultured
  • Enzyme Activation
  • Female
  • Leukemia / microbiology
  • Leukemia / veterinary
  • Leukemia Virus, Bovine / drug effects
  • Leukemia Virus, Bovine / physiology*
  • Leukocytes, Mononuclear / enzymology
  • Leukocytes, Mononuclear / microbiology
  • Lipopolysaccharides / metabolism
  • Lymphocyte Activation
  • Protein Kinase C / antagonists & inhibitors
  • Protein Kinase C / metabolism*
  • Tetradecanoylphorbol Acetate / pharmacology
  • Viral Envelope Proteins / metabolism
  • Viral Proteins / metabolism
  • Virus Replication / drug effects

Substances

  • Lipopolysaccharides
  • Viral Envelope Proteins
  • Viral Proteins
  • Protein Kinase C
  • Tetradecanoylphorbol Acetate