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.

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.

• Authors: Marilène Halin, Estelle Douceron, Isabelle Clerc, Chloé Journo, Nga Ling Ko, Sébastien Landry, Edward L Murphy, Antoine Gessain, Isabelle Lemasson, Jean-Michel Mesnard, Benoît Barbeau, Renaud Mahieux
• Journal: Blood (Blood) Vol. 114 Issue 12 Pg. 2427-38 (Sep 17 2009) ISSN: 1528-0020 [Electronic] United States
• PMID: 19602711 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Basic-Leucine Zipper Transcription Factors
• Gene Products, tax
• RNA, Antisense
• RNA, Messenger
• Viral Proteins
• tax protein, Human T-lymphotrophic virus 2
• Luciferases

Topics

• Adult
• Aged
• Aged, 80 and over
• Base Sequence
• Basic-Leucine Zipper Transcription Factors (genetics)
• Blotting, Northern
• Blotting, Western
• Female
• Fluorescent Antibody Technique
• Gene Expression Regulation, Viral
• Gene Products, tax (genetics, metabolism)
• Human T-lymphotropic virus 2 (physiology)
• Humans
• Immunoenzyme Techniques
• Immunoprecipitation
• Jurkat Cells
• Luciferases (genetics, metabolism)
• Middle Aged
• Molecular Sequence Data
• Promoter Regions, Genetic
• RNA Splicing (genetics)
• RNA, Antisense (genetics, metabolism)
• RNA, Messenger (genetics, metabolism)
• Reverse Transcriptase Polymerase Chain Reaction
• Sequence Homology, Nucleic Acid
• Transcription, Genetic
• Transfection
• Viral Proteins (genetics, metabolism)