[Adult T-cell leukemia induced by HTLV-1: before and after HBZ].
Adult T-cell leukemia (ATL) is an often fatal leukemia of CD4+ T lymphocytes associated with a complex retrovirus, human T-cell leukemia virus type 1 (HTLV-1). Although the viral Tax protein is involved in the proliferation of infected cells during the preleukemic stages, Tax expression is not systematically detected in primary leukemic cells. In 2002, we described the characterization of a novel viral protein that we have termed HBZ for HTLV-1 bZIP factor. This viral factor is encoded on the antisense strand of HTLV-1 proviral DNA, demonstrating the existence of antisense transcription from a promoter located in the 3' LTR. HBZ can negatively control the expression of the other viral proteins by blocking the interaction between Tax and ATF/CREB factors and the recruitment of CBP/p300 by Tax on the promoter. Moreover, recent studies found that the viral HBZ gene was always expressed in leukemic cells, suggesting its involvement in the progression of the infected cells towards malignancy.
Duc Dodon
Madeleine
M
virologie humaine, Inserm U758, 69364, Lyon Cedex 07, France.
Mesnard
Jean-Michel
JM
Barbeau
Benoît
B
D051696:Activating Transcription Factors / Q000378:metabolism; D000818:Animals; D050976:Basic-Leucine Zipper Transcription Factors / Q000235:genetics / Q000502:physiology*; D002455:Cell Division; D002472:Cell Transformation, Viral / Q000235:genetics*; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D015967:Gene Expression Regulation, Viral; D016356:Gene Products, tax / Q000378:metabolism; D016355:Genes, pX; D015368:Human T-lymphotropic virus 1 / Q000235:genetics / Q000472:pathogenicity / Q000502:physiology*; D006801:Humans; D016350:Leucine Zippers / Q000235:genetics / Q000502:physiology; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000235:genetics / Q000276:immunology / Q000821:virology*; D008957:Models, Genetic; D011401:Promoter Regions, Genetic / Q000235:genetics; D011533:Proviruses / Q000235:genetics; D034741:RNA, Small Interfering / Q000494:pharmacology; D011817:Rabbits; D012191:Retroviridae Proteins; D020079:Terminal Repeat Sequences / Q000235:genetics; D014158:Transcription, Genetic / Q000187:drug effects / Q000235:genetics; D014764:Viral Proteins / Q000235:genetics / Q000502:physiology*; D050880:p300-CBP Transcription Factors / Q000378:metabolism
D051696:Activating Transcription Factors; D050976:Basic-Leucine Zipper Transcription Factors; C115163:CREB1 protein, human; D017362:Cyclic AMP Response Element-Binding Protein; D016356:Gene Products, tax; C479751:HBZ protein, human T-cell leukemia virus type I; D034741:RNA, Small Interfering; D012191:Retroviridae Proteins; D014764:Viral Proteins; C514970:tax protein, Human T-lymphotrophic virus 1; D050880:p300-CBP Transcription Factors