title: Kinetics and intracellular compartmentalization of HTLV-1 gene expression: nuclear retention of HBZ mRNAs.
abstract: Human T-cell leukemia virus type 1 (HTLV-1) codes for 9 alternatively spliced transcripts and 2 major regulatory proteins named Tax and Rex that function at the transcriptional and posttranscriptional levels, respectively. We investigated the temporal sequence of HTLV-1 gene expression in primary cells from infected patients using splice site-specific quantitative RT-PCR. The results indicated a two-phase kinetics with the tax/rex mRNA preceding expression of other viral transcripts. Analysis of mRNA compartmentalization in cells transfected with HTLV-1 molecular clones demonstrated the strict Rex-dependency of the two-phase kinetics and revealed strong nuclear retention of HBZ mRNAs, supporting their function as noncoding transcripts. Mathematical modeling underscored the importance of a delay between the functions of Tax and Rex, which was supported by experimental evidence of the longer half-life of Rex. These data provide evidence for a temporal pattern of HTLV-1 expression and reveal major differences in the intracellular compartmentalization of HTLV-1 transcripts.
authors.affiliation: Department of Oncology and Surgical Sciences, University of Padova, Padova, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Rende
authors.forename: Ilaria
authors.initials: I
authors.lastname: Cavallari
authors.forename: Alberto
authors.initials: A
authors.lastname: Corradin
authors.forename: Micol
authors.initials: M
authors.lastname: Silic-Benussi
authors.forename: Frederic
authors.initials: F
authors.lastname: Toulza
authors.forename: Gianna M
authors.initials: GM
authors.lastname: Toffolo
authors.forename: Yuetsu
authors.initials: Y
authors.lastname: Tanaka
authors.forename: Steven
authors.initials: S
authors.lastname: Jacobson
authors.forename: Graham P
authors.initials: GP
authors.lastname: Taylor
authors.forename: Donna M
authors.initials: DM
authors.lastname: D'Agostino
authors.forename: Charles R M
authors.initials: CR
authors.lastname: Bangham
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Ciminale
mesh_terms: D050976:Basic-Leucine Zipper Transcription Factors / Q000235:genetics*; D002451:Cell Compartmentation; D002467:Cell Nucleus / Q000235:genetics / Q000821:virology; D015870:Gene Expression; D016370:Gene Products, rex / Q000235:genetics / Q000378:metabolism; D016356:Gene Products, tax / Q000235:genetics / Q000378:metabolism; D005814:Genes, Viral; D015490:HTLV-I Infections / Q000235:genetics* / Q000821:virology*; D015368:Human T-lymphotropic virus 1 / Q000235:genetics*; D006801:Humans; D007700:Kinetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012367:RNA, Viral / Q000235:genetics / Q000378:metabolism; D012191:Retroviridae Proteins; D014764:Viral Proteins / Q000235:genetics*
chemical_list: D050976:Basic-Leucine Zipper Transcription Factors; D016370:Gene Products, rex; 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; C514844:rex Protein, Human T-lymphotropic virus 1; C514970:tax protein, Human T-lymphotrophic virus 1