title: The HTLV-1 hbz antisense gene indirectly promotes tax expression via down-regulation of p30(II) mRNA.
abstract: Human T-cell leukemia virus type 1 (HTLV-1) basic leucine zipper factor (HBZ) is transcribed from the antisense genomic DNA strand and functions differently in its RNA and protein forms. To distinguish between the roles of hbz mRNA and HBZ protein, we generated mutants in a proviral clone that specifically disrupt the hbz gene product. A proviral clone with a splice acceptor mutation that disrupts expression of the predominant hbz mRNA resulted in lower levels of tax mRNA. Heterologous hbz expression restored Tax activity in cells expressing this mutant clone. In contrast, proviral mutants that disrupt HBZ protein did not affect levels of tax mRNA. Expression of hbz resulted in lower levels of p30(II) mRNA. Mutation of p30(II) overcame the effects of the splice acceptor mutation of hbz, and restored tax expression. Thus, there is a complex interplay of viral regulatory proteins controlling levels of HTLV-1 gene expression.
authors.affiliation: Division of Molecular Oncology, Washington University School of Medicine, St. Louis, MO, USA.
authors.forename: Gunjan
authors.initials: G
authors.lastname: Choudhary
authors.forename: Lee
authors.initials: L
authors.lastname: Ratner
mesh_terms: D050976:Basic-Leucine Zipper Transcription Factors / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D015967:Gene Expression Regulation, Viral; D055786:Gene Knockout Techniques; D016356:Gene Products, tax / Q000096:biosynthesis*; D005816:Genetic Complementation Test; D015368:Human T-lymphotropic virus 1 / Q000502:physiology*; D006801:Humans; D011533:Proviruses / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis; D012367:RNA, Viral / Q000096:biosynthesis; D012191:Retroviridae Proteins / Q000096:biosynthesis*; D014158:Transcription, Genetic; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D050976:Basic-Leucine Zipper Transcription Factors; D016356:Gene Products, tax; C479751:HBZ protein, human T-cell leukemia virus type I; D012333:RNA, Messenger; D012367:RNA, Viral; D012191:Retroviridae Proteins; D014764:Viral Proteins; C514970:tax protein, Human T-lymphotrophic virus 1; C072814:tof protein, Human T-lymphotropic virus 1