Activation of the GM-CSF promoter by HTLV-I and -II tax proteins.
Production of granulocyte-macrophage colony-stimulating factor (GM-CSF) by normal T lymphocytes requires activation by antigen, mitogen or lectin, whereas T-cell lines transformed by human T-cell leukemia virus type I (HTLV-I) or type II (HTLV-II) constitutively produce high levels of GM-CSF. Using transient cotransfection assays, we demonstrate that introduction of the tax gene of either HTLV-I or HTLV-II is sufficient to activate GM-CSF promoter constructs in an unstimulated T-cell line. The GM-CSF 5' flanking sequences previously shown to be sufficient for GM-CSF induction following T-cell activation are also sufficient for activation by the HTLV tax proteins. The sequences required for trans-activation of GM-CSF are distinct from those required for the activation of other T-cell-inducible genes (IL-2R alpha, IL-2) by tax, suggesting that tax can have pleiotropic effects on gene expression in T cells. Constitutive GM-CSF production by HTLV-infected T cells may therefore be due to trans-activation of its promoter by tax. Expression of GM-CSF by HTLV-I infected lymphocytes may be important in the granulocytosis and eosinophilia frequently seen in patients with HTLV-I-induced adult T-cell leukemia/lymphoma.
Nimer
S D
SD
Department of Medicine, UCLA School of Medicine 90024-1678.
Gasson
J C
JC
Hu
K
K
Smalberg
I
I
Williams
J L
JL
Chen
I S
IS
Rosenblatt
J D
JD
D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D015500:Chloramphenicol O-Acetyltransferase / Q000235:genetics; D003115:Colony-Stimulating Factors / Q000096:biosynthesis / Q000235:genetics*; D004279:DNA, Viral; D005786:Gene Expression Regulation; D016356:Gene Products, tax; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D006133:Growth Substances / Q000096:biosynthesis / Q000235:genetics*; D015486:HTLV-I Antigens / Q000235:genetics*; D015368:Human T-lymphotropic virus 1 / Q000235:genetics*; D015367:Human T-lymphotropic virus 2 / Q000235:genetics*; D006801:Humans; D011401:Promoter Regions, Genetic; D011971:Receptors, Immunologic / Q000235:genetics; D012191:Retroviridae Proteins / Q000235:genetics*; D013601:T-Lymphocytes / Q000378:metabolism / Q000382:microbiology*; D015534:Trans-Activators; D014157:Transcription Factors / Q000235:genetics*; D014162:Transfection
D003115:Colony-Stimulating Factors; D004279:DNA, Viral; D016356:Gene Products, tax; D006133:Growth Substances; D015486:HTLV-I Antigens; D011971:Receptors, Immunologic; D012191:Retroviridae Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D015500:Chloramphenicol O-Acetyltransferase