A MOLECULAR MECHANISM FOR HUMAN T-CELL LEUKEMIA-VIRUS LATENCY AND TAXTRANSACTIVATION

The human T cell leukemia virus type I (HTLV-I) is the causative agent of an aggressive T-cell malignancy in humans. While the virus appears to maintain a state of latency in most infected cells, high level vir ion production is an essential step in the HTLV-I Life cycle, The vira lly-encoded Tax protein, a potent activator of gene expression, is bel ieved to control the switch from latency to replication. Tax stimulati on of HTLV-I transcription is mediated through cellular activating tra nscription factor/cAMP response element binding proteins, which bind t he three al-base pair (bp) repeat viral enhancer elements, In this rep ort, we show that viral latency may result from a highly unstable inte raction between CREB and the HTLV-I 21-bp repeats, resulting in rapid dissociation of CREB from the viral promoter. In the presence Tax, the dissociation rate of CREB from a 21-bp repeat element is decreased. T his stabilization is highly specific, requiring the amino-terminal reg ion of CREB and appropriate 21-bp repeat sequences. me suggest that Ta x stabilization of CREB binding to the viral promoter leads to an incr ease in gene expression, possibly providing the switch from latency to high level replication of the virus.