Infection with human T-lymphotropic viruses leads to constitutive expression of leukemia inhibitory factor and interleukin-6.
Leukemia inhibitory factor (LIF), similar to interleukin-6 (IL-6), is a glycoprotein growth factor and differentiation regulator that has pleiotropic activity in several cellular systems. Recent reports of constitutive IL-6 production from spontaneously proliferating cells from human T-cell leukemia virus (HTLV)-infected individuals led us to examine the expression of IL-6 and LIF during HTLV infection. In vitro infection of peripheral blood lymphocytes with HTLV-I was associated with production of both soluble LIF and IL-6 in conjunction with the increasing HTLV antigen concentration. Northern blot analysis of T-cell lines generated from individuals infected with HTLV-I (MT-2, HuT-102, FS, EG, SP) and HTLV-II (Mo-T, H2A, H2E) demonstrated a marked increase in constitutive expression of LIF and IL-6 transcripts, as compared with uninfected cell lines (HuT-78, Jurkat). The constitutive expression of LIF and IL-6 was independent of presence of IL-2 in the culture medium, as both IL-2-independent (MT-2, HuT-102, SP, Mo-T) and IL-2-dependent (FS, EG, H2A, H2E) cell lines expressed LIF and IL-6 transcripts. Furthermore, LIF and IL-6 RNA expression in an HTLV-I-infected cell line (MT-2) was enhanced by phorbol ester stimulation via mechanisms that appear to be dependent on the posttranscriptional regulatory controls. These results show that both LIF and IL-6 are produced by HTLV-I- and HTLV-II-infected cells, which could potentially alter the transcriptional regulation of HTLV gene expression by inducing certain early response genes.
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Retrovirus Diseases Branch, National Center for Infectious Diseases, Centers for Disease Control, Atlanta, GA 30333.
Rudolph
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Buckner
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Pardi
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Hooper
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D002460:Cell Line; D006800:Deltaretrovirus Infections / Q000097:blood / Q000378:metabolism*; D006131:Growth Inhibitors / Q000096:biosynthesis / Q000378:metabolism*; D015490:HTLV-I Infections / Q000378:metabolism; D015491:HTLV-II Infections / Q000378:metabolism; D006801:Humans; D015850:Interleukin-6 / Q000096:biosynthesis / Q000378:metabolism*; D053605:Leukemia Inhibitory Factor; D008222:Lymphokines / Q000096:biosynthesis / Q000187:drug effects / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D006131:Growth Inhibitors; D015850:Interleukin-6; C507837:LIF protein, human; D053605:Leukemia Inhibitory Factor; D008222:Lymphokines; D013755:Tetradecanoylphorbol Acetate