Human T-lymphotropic virus type-1 p30 alters cell cycle G2 regulation of T lymphocytes to enhance cell survival

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dc.creator Datta, Antara
dc.creator Silverman, Lee
dc.creator Phipps, Andrew J.
dc.creator Hiraragi, Hajime
dc.creator Ratner, Lee
dc.creator Lairmore, Michael D. 2010-11-29T16:49:31Z 2010-11-29T16:49:31Z 2007-07-16
dc.identifier.citation Antara Datta et al, "Human T-lymphotropic virus type-1 p30 alters cell cycle G2 regulation of T lymphocytes to enhance cell survival," Retrovirology 4 (2007), doi:10.1186/1742-4690-4-49, en_US
dc.identifier.issn 1742-4690
dc.description.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 Taxresponsive 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. Conclusion: 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 Tcell survival. en_US
dc.language.iso en_US en_US
dc.publisher BioMed Central en_US
dc.title Human T-lymphotropic virus type-1 p30 alters cell cycle G2 regulation of T lymphocytes to enhance cell survival en_US
dc.type Article en_US
dc.identifier.doi 10.1186/1742-4690-4-49
dc.identifier.osuauthor datta.15
dc.identifier.osuauthor lairmore.1 Attribution 3.0 Unported en_US
dc.rights.ccuri en_US
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Attribution 3.0 Unported