title: Human T lymphotropic virus type-1 p30II alters cellular gene expression to selectively enhance signaling pathways that activate T lymphocytes.
abstract: BACKGROUND
  Human T-lymphotropic virus type-1 (HTLV-1) is a deltaretrovirus that causes adult T-cell leukemia/lymphoma and is implicated in a variety of lymphocyte-mediated disorders. HTLV-1 contains both regulatory and accessory genes in four pX open reading frames. pX ORF-II encodes two proteins, p13II and p30II, which are incompletely defined in the virus life cycle or HTLV-1 pathogenesis. Proviral clones of the virus with pX ORF-II mutations diminish the ability of the virus to maintain viral loads in vivo. Exogenous expression of p30II differentially modulates CREB and Tax-responsive element-mediated transcription through its interaction with CREB-binding protein/p300 and represses tax/rex RNA nuclear export.
  
  
  RESULTS
  Herein, we further characterized the role of p30II in regulation of cellular gene expression, using stable p30II expression system employing lentiviral vectors to test cellular gene expression with Affymetrix U133A arrays, representing approximately 33,000 human genes. Reporter assays in Jurkat T cells and RT-PCR in Jurkat and primary CD4+ T-lymphocytes were used to confirm selected gene expression patterns. Our data reveals alterations of interrelated pathways of cell proliferation, T-cell signaling, apoptosis and cell cycle in p30II expressing Jurkat T cells. In all categories, p30II appeared to be an overall repressor of cellular gene expression, while selectively increasing the expression of certain key regulatory genes.
  
  
  CONCLUSIONS
  We are the first to demonstrate that p30II, while repressing the expression of many genes, selectively activates key gene pathways involved in T-cell signaling/activation. Collectively, our data suggests that this complex retrovirus, associated with lymphoproliferative diseases, relies upon accessory gene products to modify cellular environment to promote clonal expansion of the virus genome and thus maintain proviral loads in vivo.
authors.affiliation: Center for Retrovirus Research, Department of Veterinary Biosciences, The Ohio State University, Columbus, Ohio 43210, USA. bindhu_michael@merck.com
authors.forename: Bindhu
authors.initials: B
authors.lastname: Michael
authors.forename: Amrithraj M
authors.initials: AM
authors.lastname: Nair
authors.forename: Hajime
authors.initials: H
authors.lastname: Hiraragi
authors.forename: Lei
authors.initials: L
authors.lastname: Shen
authors.forename: Gerold
authors.initials: G
authors.lastname: Feuer
authors.forename: Kathleen
authors.initials: K
authors.lastname: Boris-Lawrie
authors.forename: Michael D
authors.initials: MD
authors.lastname: Lairmore
mesh_terms: D017209:Apoptosis; D005786:Gene Expression Regulation; D015368:Human T-lymphotropic virus 1 / Q000145:classification / Q000235:genetics / Q000276:immunology*; D006801:Humans; D019169:Jurkat Cells; D008213:Lymphocyte Activation; D016328:NF-kappa B / Q000378:metabolism; D016366:Open Reading Frames; D015398:Signal Transduction / Q000276:immunology; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000821:virology; D014158:Transcription, Genetic
chemical_list: D016328:NF-kappa B