Constitutive expression of various chemokine genes in human T-cell lines infected with human T-cell leukemia virus type 1: role of the viral transactivator Tax.
We examined the genetic expression of 2 CXC chemokines (IL-8, IP-10), 5 CC chemokines (MCP-1, MIP-lalpha, MIP-1beta, RANTES, 1309) and 1 C chemokine (SCM-1/lymphotactin/ATAC) in various human T-cell lines. By Northern blot analysis, HTLV-1-positive T-cell lines were found to express a number of chemokine genes at variable levels and in different combinations. However, none of the chemokine genes was expressed in HTLV-1-negative T-cell lines. We further confirmed secretion of 3 chemokines (IL-8, MIP-1alpha and RANTES) by some HTLV-1-positive T-cell lines. To examine the role of the HTLV-1-encoded transactivator Tax in the induction of these chemokine genes, we used JPX-9 and JPX-M, which were stably transformed with tax and non-functional tax, respectively, under the control of a metallothionein promoter. Induction of tax in JPX-9 with Cd2+ was accompanied by rapid induction of IL-8, IP-10, MIP-1alpha, MIP-1beta, 1309 and SCM-1 as determined by reverse transcription PCR. No such induction was seen in JPX-M. We thus suggest that Tax is, at least in part, responsible for constitutive expression of certain chemokine genes in HTLV-1-infected T cells. Aberrant production of various chemokines by HTLV-1- infected T cells may impact on the pathophysiology of HTLV-1-associated diseases.
Baba
M
M
Shionogi Institute for Medical Science, Osaka, Japan.
Imai
T
T
Yoshida
T
T
Yoshie
O
O
D002478:Cells, Cultured; D018925:Chemokines / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D015967:Gene Expression Regulation, Viral; D016356:Gene Products, tax / Q000502:physiology*; D016355:Genes, pX; D015490:HTLV-I Infections / Q000382:microbiology*; D015368:Human T-lymphotropic virus 1 / Q000235:genetics*; D006801:Humans; D012333:RNA, Messenger / Q000235:genetics; D013601:T-Lymphocytes / Q000502:physiology*; D014407:Tumor Cells, Cultured
D018925:Chemokines; D016356:Gene Products, tax; D012333:RNA, Messenger