Abstract
Retroviral gene expression generally depends on a full-length transcript that initiates in the 5′ long terminal repeat (LTR), which is either unspliced 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 is involved in the production of HBZ (HTLV-1 basic leucine zipper (bZIP) factor). HBZ is a Fos-like factor capable of inhibiting Tax-mediated activation of the HTLV-1 LTR by interacting with the cellular transcription factor cAMP-response element-binding protein (CREB) and the pleiotropic cellular coactivators p300/CBP. HBZ can also activate cellular transcription through 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 in the 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 proteins that we have termed Antisense Protein of HTLVs (APH). Like HBZ, the APH proteins are localized in the nucleus of transfected cells and repress Tax-mediated viral transcription.
Highlights
Human T-cell leukemia virus type 1 (HTLV-1) is a complex lymphotropic retrovirus classified in the Deltaretrovirus genus of the retrovirus family
Since the discovery of HBZ in 2002, accumulating evidence suggests that the development of HTLV-1 infection requires the Tax and HBZ genes, whose expression is respectively controlled by the
Cells highly expressing HTLV-1 proteins are eliminated by the humoral response and CTL
Summary
Human T-cell leukemia virus type 1 (HTLV-1) is a complex lymphotropic retrovirus classified in the Deltaretrovirus genus of the retrovirus family. The existence of antisense transcription in HTLV-1 was demonstrated for the first time in 1989 through Northern blot analysis of RNA extracted from an HTLV-1-infected cell line [7] It is only 13 years later that we provided the first evidence of a protein termed HTLV-1 basic leucine zipper (bZIP) factor (HBZ) produced from an HTLV-1 antisense transcript [8]. These experiments showed that the antisense transcript was spliced and produced a major spliced form with the ATG initiation codon located in exon 1 in the 3' LTR segment These results were confirmed by other teams using different approaches [10,11]. Processing of the HBZ transcript and addition of the polyA tail [9,11]
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