Inhibition of human T-lymphotropic virus type I gene expression by the Streptomyces-derived substance EM2487.

Abstract

EM2487, a Streptomyces-derived substance, has previously been shown to inhibit HIV-1 replication in both acutely and chronically infected cells. In this study, we found that EM2487 was also a selective inhibitor of human T-lymphotropic virus type I (HTLV-I) replication in persistently infected cells. Its 50% effective concentrations for HTLV-I p19 antigen production were 3.6 and 1.2 microM in MT-2 and MT-4 cells, respectively. However, the compound did not reduce cell proliferation and viability at these concentrations. The 50% cytotoxic concentrations of EM2487 were 30.6 and 5.7 microM in MT-2 and MT-4 cells, respectively. The compound also displayed selective inhibition of HTLV-I production in peripheral blood mononuclear cells obtained from patients with HTLV-I-associated myelopathy/tropical spastic paraparesis. Quantitative reverse transcription PCR analysis revealed that EM2487 selectively suppressed HTLV-I mRNA synthesis in MT-2 cells in a dose-dependent fashion. However, the compound did not inhibit endogenous Tax-induced HTLV-I long terminal repeat-driven reporter gene expression. Furthermore, intracellular Tax accumulation was not suppressed in MT-2 cells exposed to EM2487. These results suggest that the inhibition occurred at the viral transcription level, but it cannot be attributed to the inhibition of the Tax function.