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.
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.
Halin
Marilène
M
Département des Sciences Biologiques et Centre de recherche BioMed, Université du Québec à Montréal, QC, Canada.
Douceron
Estelle
E
Clerc
Isabelle
I
Journo
Chloé
C
Ko
Nga Ling
NL
Landry
Sébastien
S
Murphy
Edward L
EL
Gessain
Antoine
A
Lemasson
Isabelle
I
Mesnard
Jean-Michel
JM
Barbeau
Benoît
B
Mahieux
Renaud
R
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001483:Base Sequence; D050976:Basic-Leucine Zipper Transcription Factors / Q000235:genetics*; D015152:Blotting, Northern; D015153:Blotting, Western; D005260:Female; D005455:Fluorescent Antibody Technique; D015967:Gene Expression Regulation, Viral; D016356:Gene Products, tax / Q000235:genetics* / Q000378:metabolism; D015367:Human T-lymphotropic virus 2 / Q000502:physiology*; D006801:Humans; D007124:Immunoenzyme Techniques; D047468:Immunoprecipitation; D019169:Jurkat Cells; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D008875:Middle Aged; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic; D012326:RNA Splicing / Q000235:genetics*; D016372:RNA, Antisense / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012689:Sequence Homology, Nucleic Acid; D014158:Transcription, Genetic; D014162:Transfection; D014764:Viral Proteins / Q000235:genetics* / Q000378:metabolism
D050976:Basic-Leucine Zipper Transcription Factors; D016356:Gene Products, tax; D016372:RNA, Antisense; D012333:RNA, Messenger; D014764:Viral Proteins; C514971:tax protein, Human T-lymphotrophic virus 2; D008156:Luciferases