1. Human T-cell leukemia virus type 2 produces a spliced antisense transcript encoding a protein that lacks a classic bZIP domain but still inhibits Tax2-mediated transcription
- Author
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Halin, Marilène, Douceron, Estelle, Clerc, Isabelle, Journo, Chloé, Ko, Nga Ling, Landry, Sébastien, Murphy, Edward L, Gessain, Antoine, Lemasson, Isabelle, Mesnard, Jean-Michel, Barbeau, Benoît, and Mahieux, Renaud
- Subjects
Cancer ,Genetics ,Rare Diseases ,Human Genome ,Hematology ,Aetiology ,2.2 Factors relating to the physical environment ,2.1 Biological and endogenous factors ,Adult ,Aged ,Aged ,80 and over ,Base Sequence ,Basic-Leucine Zipper Transcription Factors ,Blotting ,Northern ,Blotting ,Western ,Female ,Fluorescent Antibody Technique ,Gene Expression Regulation ,Viral ,Gene Products ,tax ,Human T-lymphotropic virus 2 ,Humans ,Immunoenzyme Techniques ,Immunoprecipitation ,Jurkat Cells ,Luciferases ,Middle Aged ,Molecular Sequence Data ,Promoter Regions ,Genetic ,RNA Splicing ,RNA ,Antisense ,RNA ,Messenger ,Reverse Transcriptase Polymerase Chain Reaction ,Sequence Homology ,Nucleic Acid ,Transcription ,Genetic ,Transfection ,Viral Proteins ,Cardiorespiratory Medicine and Haematology ,Clinical Sciences ,Paediatrics and Reproductive Medicine ,Immunology - Abstract
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 element binding 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.
- Published
- 2009