title: Human T-lymphotropic virus type-1 p30 alters cell cycle G2 regulation of T lymphocytes to enhance cell survival.
abstract: BACKGROUND
  Human T-lymphotropic virus type-1 (HTLV-1) causes adult T-cell leukemia/lymphoma and is linked to a number of lymphocyte-mediated disorders. HTLV-1 contains both regulatory and accessory genes in four pX open reading frames. pX ORF-II encodes two proteins, p13 and p30, whose roles are still being defined in the virus life cycle and in HTLV-1 virus-host cell interactions. Proviral clones of HTLV-1 with pX ORF-II mutations diminish the ability of the virus to maintain viral loads in vivo. p30 expressed exogenously differentially modulates CREB and Tax-responsive element-mediated transcription through its interaction with CREB-binding protein/p300 and while acting as a repressor of many genes including Tax, in part by blocking tax/rex RNA nuclear export, selectively enhances key gene pathways involved in T-cell signaling/activation.
  
  
  RESULTS
  Herein, we analyzed the role of p30 in cell cycle regulation. Jurkat T-cells transduced with a p30 expressing lentivirus vector accumulated in the G2-M phase of cell cycle. We then analyzed key proteins involved in G2-M checkpoint activation. p30 expression in Jurkat T-cells resulted in an increase in phosphorylation at serine 216 of nuclear cell division cycle 25C (Cdc25C), had enhanced checkpoint kinase 1 (Chk1) serine 345 phosphorylation, reduced expression of polo-like kinase 1 (PLK1), diminished phosphorylation of PLK1 at tyrosine 210 and reduced phosphorylation of Cdc25C at serine 198. Finally, primary human lymphocyte derived cell lines immortalized by a HTLV-1 proviral clone defective in p30 expression were more susceptible to camptothecin induced apoptosis. Collectively these data are consistent with a cell survival role of p30 against genotoxic insults to HTLV-1 infected lymphocytes.
  
  
  CONCLUSIONS
  Collectively, our data are the first to indicate that HTLV-1 p30 expression results in activation of the G2-M cell cycle checkpoint, events that would promote early viral spread and T-cell survival.
authors.affiliation: Center for Retrovirus Research, The Ohio State University, Columbus, Ohio, USA. datta.15@osu.edu
authors.forename: Antara
authors.initials: A
authors.lastname: Datta
authors.forename: Lee
authors.initials: L
authors.lastname: Silverman
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Phipps
authors.forename: Hajime
authors.initials: H
authors.lastname: Hiraragi
authors.forename: Lee
authors.initials: L
authors.lastname: Ratner
authors.forename: Michael D
authors.initials: MD
authors.lastname: Lairmore
mesh_terms: D017209:Apoptosis / Q000502:physiology; D018797:Cell Cycle Proteins / Q000378:metabolism; D002460:Cell Line; D002470:Cell Survival / Q000502:physiology; D016195:G2 Phase / Q000235:genetics* / Q000276:immunology; D016355:Genes, pX; D015368:Human T-lymphotropic virus 1 / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D019169:Jurkat Cells; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D010766:Phosphorylation; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D013601:T-Lymphocytes / Q000166:cytology* / Q000378:metabolism / Q000502:physiology; D014161:Transduction, Genetic; D014162:Transfection; D014758:Viral Core Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D020687:cdc25 Phosphatases / Q000378:metabolism
chemical_list: D018797:Cell Cycle Proteins; D014758:Viral Core Proteins; C517009:CDC25C protein, human; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D020687:cdc25 Phosphatases