Regulation of the human interleukin-2 receptor α chain promoter: Activation of a nonfunctional promoter by the transactivator gene of HTLV-I

Cross, S L; Feinberg, Mark B.; Wolf, Julie B.; Holbrook, Nikki J.; Wong‐Staal, Flossie; Leonard, Warren J.

doi:10.1016/0092-8674(87)90754-9

Cited by 414 publications

(243 citation statements)

References 36 publications

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“…There are reports of in vitro activation of the IL-2 promoter by HTLV-1 Tax, however, we found a very small magnitude of activation, when compared with many other Tax-responsive genes, such as IL-2Ra and PTHrP (Inoue et al, 1986;Leung and Nabel, 1988;Watanabe et al, 1990; and data not shown). These observations are consistent with ®ndings of other researchers (Siekevitz et al, 1987;Cross et al, 1987). Thus, although the hypothesis that proliferation of HTLV-1-infected cells is mediated by activation of the IL-2/IL-2R loop is attractive, more concrete evidence to support this notion is needed.…”

Section: Discussionsupporting

confidence: 80%

Involvement of IL-2/IL-2R system activation by parasite antigen in polyclonal expansion of CD4+25+ HTLV-1-infected T-cells in human carriers of both HTLV-1 and S. stercoralis

et al. 2002

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The intermediate state of HTLV-1 infection, often found in individuals dually infected with Strongyloides stercoralis (S. stercoralis) and HTLV-1, is assumed to be a preleukemic state of adult T-cell leukemia (ATL). To investigate the e ects of S. stercoralis superinfection on the natural history of HTLV-1 infection, we characterized peripheral blood samples of these individuals in Okinawa, Japan, an endemic area for both HTLV-1 and S. stercoralis and we studied e ects of the parasite antigen on T-cells. The dually infected individuals showed a signi®cantly higher provirus load and an increase in CD4 + 25 + T cell population, with a signi®cant, positive correlation. This increase was attributable to polyclonal expansion of HTLV-1-infected cells, as demonstrated by inverse-long PCR analysis of the integration sites. S. stercoralis antigen activated the IL-2 promoter in reporter gene assays, induced production of IL-2 by PBMC in vitro, and supported growth of IL-2 dependent cell lines immortalized by HTLV-1 infection or the transduction of Tax. Taken collectively, these results indicate that S. stercoralis infection induces polyclonal expansion of HTLV-1-infected cells by activating the IL-2/IL-2R system in dually infected carriers, an event which may be a precipitating factor for ATL and in¯ammatory diseases.

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Section: Discussionsupporting

confidence: 80%

Involvement of IL-2/IL-2R system activation by parasite antigen in polyclonal expansion of CD4+25+ HTLV-1-infected T-cells in human carriers of both HTLV-1 and S. stercoralis

et al. 2002

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“…This is due to the e ect of the viral Tax oncoprotein, which keeps the infected CD4 T lymphocyte cycling (Cross et al, 1987;Duyao et al, 1992;Fujii et al, 1991;Inoue et al, 1986;Suzuki et al, 1996). In addition, through the inactivation of some DNA repair functions of the host cell (Jeang et al, 1990;Jin et al, 1998;Kao and Marriott, 1999;Philpott and Buehring, 1999; PiseMasison et al, 1998), Tax exerts a mutagenic e ect in vitro (Miyake et al, 1999).…”

Section: Discussionmentioning

confidence: 99%

High circulating proviral load with oligoclonal expansion of HTLV-1 bearing T cells in HTLV-1 carriers with strongyloidiasis

et al. 2000

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Adult T cell leukemia (ATLL) develops in 3 ± 5% of HTLV-1 carriers after a long period of latency during which a persistent polyclonal expansion of HTLV-1 infected lymphocytes is observed in all individuals. This incubation period is signi®cantly shortened in HTLV-1 carrier with Strongyloides stercoralis (Ss) infection, suggesting that Ss could be a cofactor of ATLL. As an increased T cell proliferation at the asymptomatic stage of HTLV-1 infection could increase the risk of malignant transformation, the e ect of Ss infection on infected T lymphocytes was assessed in vivo in HTLV-1 asymptomatic carriers. After real-time quantitative PCR, the mean circulating HTLV-1 proviral load was more than ®ve times higher in HTLV-1 carriers with stongyloidiasis than in HTLV-1+ individuals without Ss infection (P50.009). This increased proviral load was found to result from the extensive proliferation of a restricted number of infected clones, i.e. from oligoclonal expansion, as evidenced by the semiquantitative ampli®-cation of HTLV-1¯anking sequences. The positive e ect of Ss on clonal expansion was reversible under e ective treatment of strongyloidiasis in one patient with parasitological cure whereas no signi®cant modi®cation of the HTLV-1 replication pattern was observed in an additional case with strongyloidiasis treatment failure. Therefore, Ss stimulates the oligoclonal proliferation of HTLV-1 infected cells in HTLV-1 asymptomatic carriers in vivo. This is thought to account for the shortened period of latency observed in ATLL patients with strongyloidiasis. Oncogene (2000) 19, 4954 ± 4960.

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“…Tax has several effects on the IL-2 pathway that may explain this observation. Tax has been shown to transactivate both the IL-2 and IL-2Ra promoters through an NF-kB-like DNA element, leading to increased secretion of IL-2 and expression of the high-affinity IL-2R on the surface of infected cells (Inoue et al, 1986;Cross et al, 1987;Maruyama et al, 1987;Siekevitz et al, 1987;Ballard et al, 1988;Ruben et al, 1988;Leung and Nabel, 1988). Moreover, IL-2-independent HTLV-I-infected T cells have a constitutively activated JAK-STAT pathway, which is involved in IL-2R signal transduction.…”

Section: Cell-cycle Dysregulationmentioning

confidence: 99%

Cellular Transformation by the HTLV-I Tax Protein, a Jack-of-All-Trades

2003

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Regulation of the human interleukin-2 receptor α chain promoter: Activation of a nonfunctional promoter by the transactivator gene of HTLV-I

Cited by 414 publications

References 36 publications

Involvement of IL-2/IL-2R system activation by parasite antigen in polyclonal expansion of CD4+25+ HTLV-1-infected T-cells in human carriers of both HTLV-1 and S. stercoralis

Involvement of IL-2/IL-2R system activation by parasite antigen in polyclonal expansion of CD4+25+ HTLV-1-infected T-cells in human carriers of both HTLV-1 and S. stercoralis

High circulating proviral load with oligoclonal expansion of HTLV-1 bearing T cells in HTLV-1 carriers with strongyloidiasis

Cellular Transformation by the HTLV-I Tax Protein, a Jack-of-All-Trades

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