HTLV-I antisense transcripts initiating in the 3'LTR are alternatively spliced and polyadenylated.
BACKGROUND
Antisense transcription in retroviruses has been suggested for both HIV-1 and HTLV-I, although the existence and coding potential of these transcripts remain controversial. Thorough characterization is required to demonstrate the existence of these transcripts and gain insight into their role in retrovirus biology.


RESULTS
This report provides the first complete characterization of an antisense retroviral transcript that encodes the previously described HTLV-I HBZ protein. In this study, we show that HBZ-encoding transcripts initiate in the 3' long terminal repeat (LTR) at several positions and consist of two alternatively spliced variants (SP1 and SP2). Expression of the most abundant HBZ spliced variant (SP1) could be detected in different HTLV-I-infected cell lines and importantly in cellular clones isolated from HTLV-I-infected patients. Polyadenylation of HBZ RNA occurred at a distance of 1450 nucleotides downstream of the HBZ stop codon in close proximity of a typical polyA signal. We have also determined that translation mostly initiates from the first exon located in the 3' LTR and that the HBZ isoform produced from the SP1 spliced variant demonstrated inhibition of Tax and c-Jun-dependent transcriptional activation.


CONCLUSIONS
These results conclusively demonstrate the existence of antisense transcription in retroviruses, which likely plays a role in HTLV-I-associated pathogenesis through HBZ protein synthesis.
Cavanagh
Marie-Hélène
MH
Centre de Recherche en Infectiologie, Centre Hospitalier Universitaire de Québec, Pavillon CHUL, Québec, G1V 4G2, Canada. marie-helene.cavanagh@crchul.ulaval.ca
Landry
Sébastien
S
Audet
Brigitte
B
Arpin-André
Charlotte
C
Hivin
Patrick
P
Paré
Marie-Eve
ME
Thête
Julien
J
Wattel
Eric
E
Marriott
Susan J
SJ
Mesnard
Jean-Michel
JM
Barbeau
Benoit
B
D017398:Alternative Splicing; D050976:Basic-Leucine Zipper Transcription Factors / Q000235:genetics*; D016373:DNA, Antisense / Q000235:genetics*; D015368:Human T-lymphotropic virus 1 / Q000235:genetics*; D016350:Leucine Zippers / Q000235:genetics; D011061:Poly A / Q000235:genetics*; D012191:Retroviridae Proteins; D020079:Terminal Repeat Sequences / Q000235:genetics*; D014158:Transcription, Genetic; D014764:Viral Proteins / Q000235:genetics*
D050976:Basic-Leucine Zipper Transcription Factors; D016373:DNA, Antisense; C479751:HBZ protein, human T-cell leukemia virus type I; D012191:Retroviridae Proteins; D014764:Viral Proteins; D011061:Poly A