Journal
BLOOD
Volume 114, Issue 12, Pages 2427-2438Publisher
AMER SOC HEMATOLOGY
DOI: 10.1182/blood-2008-09-179879
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Funding
- Inserm
- Ecole Normale Superieure de Lyon
- Ministere de la Recherche
- Croucher Foundation
- Agence Nationale de Recherches sur le Sida et les hepatites virales
- Cancer Research Society
- institutional Hydro-Quebec scholarship
- US National Heart, Lung, and Blood Institute [R01-HL-62235, K24-HL-75036]
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Human T-cell leukemia virus type 1 (HTLV-1) and type 2 (HTLV-2) retroviruses infect T lymphocytes. The minus strand of the HTLV-1 genome encodes HBZ, a protein that could play a role in the development of leukemia in infected patients. Herein, we demonstrate that the complementary strand of the HTLV-2 genome also encodes a protein that we named APH-2 for antisense protein of HTLV-2. APH-2 mRNA is spliced, polyadenylated, and initiates in the 3'-long terminal repeat at different positions. This transcript was detected in all HTLV-2-infected cell lines and short-term culture of lymphocytes obtained from HTLV-2 African patients tested and in 4 of 15 HTLV-2-infected blood donors. The APH-2 protein is 183 amino acids long, is localized in the cell nucleus, and is detected in vivo. Despite the lack of a consensus basic leucine zipper domain, APH-2 interacts with cyclic adenosine monophosphate-response elementbinding protein (CREB) and represses Tax2-mediated transcription in Tax2-expressing cells and in cells transfected with an HTLV-2 molecular clone. Altogether, our results demonstrate the existence of an antisense strand-encoded protein in HTLV-2, which could represent an important player in the development of disorders, such as lymphocytosis, which is frequently observed in HTLV-2 patients. (Blood. 2009; 114: 2427-2438)
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