Abstract
Retroviral gene expression generally depends on a full-length transcript that initiates in the 5'long terminal repeat (LTR), which is eitherunspliced or alternatively spliced. We and others have demonstrated the existence of an antisense transcript initiating in the 3'LTR of the Human T-cell Leukemia Virus type 1 (HTLV-1) that isinvolved in the production of HBZ (HTLV-1 basic leucine zipper (bZIP) factor). HBZ is a Fos-like factorcapable of inhibiting Tax-mediated activation of the HTLV-1 LTRby interacting with the cellular transcription factor cAMP-response element-binding protein (CREB) and the pleiotropic cellular coactivators p300/CBP. HBZ can also activate cellular transcriptionthrough its interaction with p300/CBP. Interestingly, HBZ has also been found to promote T-lymphocyte proliferation.By down-regulating viral expression and by stimulating T-cell proliferation, HBZ could be essential inthe establishment of a chronic infection. Antisense transcription also occurs in the closely related HTLV-2 retrovirus as well as in the recently discovered HTLV-3 and HTLV-4. These antisense transcripts are also involved in the production of retroviral proteinsthat we have termedAntisenseProtein of HTLVs (APH). Like HBZ, the APH proteinsarelocalized in the nucleus of transfected cells andrepress Tax-mediated viral transcription.