A-101 The human leukemia virus-HTLV-1—persistence and pathogenesis

Abstract

The human leukemia virus HTLV-1 persists lifelong in infected people. Although the virus elicits a strong chronically activated T cell immune response to the major viral proteins Gag, Pol, Env and Tax, the genes encoding these proteins are usually silent in circulating lymphocytes. In contrast, there is a weak T cell response to the viral protein HBZ, which appears to be persistently expressed at a low level. There is recent evidence that the plus strand of the HTLV-1 provirus, which encodes the immunodominant T cell antigens, is expressed in intermittent bursts, whereas the minus strand (encoding hbzis almost constantly expressed, in all cells, at a low level. We are now investigating how HTLV-1 regulates this selective expression of the proviral plus- and minus-strands. I shall present evidence from single molecule RNA-FISH, chromosome conformation capture, small-molecule inhibitors, and transcription analysis (RNA-Seq; qRT-PCR) that specific epigenetic and metabolic factors regulate this strand-specific proviral expression. The results offer an explanation of long-standing paradoxes and unexplained observations in the biology of this pathogenic retrovirus.