HSP70 production and inhibition of cell proliferation in molt-4 T-cells after cell-to-cell transmission of HTLV-I: Effect of PGA 1

Abstract

Infection with HTLV-I is associated with leukemic transformation of mature CD4 + T lymphocytes. PGA 1, a powerful inhibitor of tumour cell proliferation, can prevent the clonal expansion of HTLV-I-infected cells following acute infection of cord blood-derived mononuclear cells. Since the antiproliferative effect of PGA 1 on HTLV-I transformed, chronically infected MT-2 cell line was associated with induction of HSP70, we have investigated the effect of PGA 1 on cell cycle progression and HSP70 production in a leukemic T-cell line (Molt-4) shortly after exposure to HTLV-I in a cell-to-cell transmission model. Rate of cell proliferation and HSP70 expression were studied within one duplication cycle of Molt-4 cells after exposure to HTLV-I. Growth of both control and virus-exposed cultures was inhibited by treatment with PGA 1 (4 μg/ml) and cell cycling was arrested preferentially at the G 1/S interphase. Synthesis of HSP70 was induced within 3 h by PGA 1 in control and virus-exposed Molt-4 cells and became undetectable from overnight onward, though the protein accumulated in the cells. The arrest of growth was observed from overnight up to 48 h so that treated cells almost missed one cycle. Interestingly, HSP70 transcript and protein persisted at remarkably high levels in Molt-4 cells exposed to HTLV-I in the absence of PGA 1, showing that HSP70 expression can be directly activated during primary infection with this human retrovirus. Moreover, in these cocultures, treatment with PGA 1 or heat shock was not able to increase further the elevated level of HSP70 found in untreated cocultures, suggesting that during the early period of the virus-transmission phase, HTLV-I could interfere with HSP70 induction by other inducers.