Inhibition of HIV type 1 Tat-mediated trans-activation by oncostatin M in HLtat cells

AIDS Res Hum Retroviruses. 1995 Nov;11(11):1355-8. doi: 10.1089/aid.1995.11.1355.

Abstract

We have tested the effect of oncostatin M (OSM) on the Tat-mediated trans-activation in a HeLa cell line (HLtat) expressing Tat, using a transfection assay with the LacZ gene under the control of the HIV-1 LTR. Oncostatin M reduced the LacZ expression by 50% at a concentration of 9.5 ng/ml (IC50), which was far below the 50% cytotoxic concentration (CC50 > 400 ng/ml). Although HLtat cells may represent an interesting model for the study of the signal transduction pathway of OSM, this cytokine did not inhibit the tumor necrosis factor (TNF)-dependent activation of the HIV LTR in Molt pNAZ cells or the Tat-mediated trans-activation in HeLa, HeLa-CD4, Hep-II, COS-7, or Jurkat-tat cells. Likewise, OSM did not show any anti-HIV-1 activity in the MT4 cell/MTT assay. Our findings with OSM indicate that, for the screening of HIV Tat inhibitors, care must be taken in selecting a system that not only emulates HIV Tat trans-activation, but is also representative for in vivo-infected cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antiviral Agents / pharmacology*
  • Cell Line
  • Gene Expression / drug effects
  • Gene Products, tat / antagonists & inhibitors
  • Gene Products, tat / genetics*
  • HIV-1 / drug effects*
  • HIV-1 / metabolism
  • HeLa Cells
  • Humans
  • Oncostatin M
  • Peptides / pharmacology*
  • Transcriptional Activation / drug effects*
  • tat Gene Products, Human Immunodeficiency Virus

Substances

  • Antiviral Agents
  • Gene Products, tat
  • OSM protein, human
  • Peptides
  • tat Gene Products, Human Immunodeficiency Virus
  • Oncostatin M