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Transformation to continuous growth of primary human T lymphocytes by human T-cell leukemia virus type I X-region genes transduced by a Herpesvirus saimiri vector.

Abstract
The role of the X region of the genome of the human T-cell leukemia virus type I (HTLV-I) in the immortalization of lymphocytes has been difficult to distinguish from its role in viral replication as this region encodes at least two genes, tax and rex, required for replication and the expression of viral proteins. To determine whether the X region does encode immortalizing functions, a fragment of the HTLV-I provirus capable of expressing known X-region proteins was inserted into the genome of a transformation-defective, replication-competent Herpesvirus saimiri. Infection of fresh mitogen-activated human cord blood and thymocytes yielded immortal T-cell lines that had the same phenotype (CD4+, CD5+, HLA class II+, interleukin 2 receptor alpha-chain +) as lymphocytes transformed by cocultivation with HTLV-I. These experiments demonstrate that the X region encodes the functions of HTLV-I that immortalize a distinct subpopulation of human T cells. The experiments also demonstrate the utility of the H. saimiri vector for the transduction of heterologous genes into human T cells.
AuthorsR Grassmann, C Dengler, I Müller-Fleckenstein, B Fleckenstein, K McGuire, M C Dokhelar, J G Sodroski, W A Haseltine
JournalProceedings of the National Academy of Sciences of the United States of America (Proc Natl Acad Sci U S A) Vol. 86 Issue 9 Pg. 3351-5 (May 1989) ISSN: 0027-8424 [Print] United States
PMID2541443 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
Chemical References
  • DNA, Viral
  • Viral Proteins
Topics
  • Cell Transformation, Neoplastic
  • Cell Transformation, Viral
  • Cloning, Molecular
  • DNA, Viral (genetics)
  • Fetal Blood (cytology)
  • Gene Expression Regulation
  • Genes, Viral
  • Genetic Vectors
  • Herpesvirus 2, Saimiriine (genetics)
  • Human T-lymphotropic virus 1 (genetics)
  • Humans
  • Nucleic Acid Hybridization
  • Phenotype
  • Plasmids
  • Promoter Regions, Genetic
  • T-Lymphocytes (cytology)
  • Transduction, Genetic
  • Transfection
  • Viral Proteins (genetics)

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