Inhibition of HIV type 1 Tat-mediated trans-activation by oncostatin M in HLtat cells.
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.
Esté
J A
JA
Rega Institute for Medical Research, Katholieke Universiteit Leuven, Belgium.
Witvrouw
M
M
Tu
J
J
Desmyter
J
J
De Clercq
E
E
Vandamme
A M
AM
D000998:Antiviral Agents / Q000494:pharmacology*; D002460:Cell Line; D015870:Gene Expression / Q000187:drug effects; D015696:Gene Products, tat / Q000037:antagonists & inhibitors / Q000235:genetics*; D015497:HIV-1 / Q000187:drug effects* / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D053683:Oncostatin M; D010455:Peptides / Q000494:pharmacology*; D015533:Transcriptional Activation / Q000187:drug effects*; D054322:tat Gene Products, Human Immunodeficiency Virus
D000998:Antiviral Agents; D015696:Gene Products, tat; C508351:OSM protein, human; D010455:Peptides; D054322:tat Gene Products, Human Immunodeficiency Virus; D053683:Oncostatin M