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    J Clin Invest. 2006 Apr;116(4):974-83.

    HTLV-1 propels untransformed CD4 lymphocytes into the cell cycle while protecting CD8 cells from death.

    Source

    Oncovirologie et Biothérapies, CNRS UMR5537- Université Claude Bernard, Centre Léon Bérard, Lyon, France.

    Abstract

    Human T cell leukemia virus type 1 (HTLV-1) infects both CD4+ and CD8+ lymphocytes, yet it induces adult T cell leukemia/lymphoma (ATLL) that is regularly of the CD4+ phenotype. Here we show that in vivo infected CD4+ and CD8+ T cells displayed similar patterns of clonal expansion in carriers without malignancy. Cloned infected cells from individuals without malignancy had a dramatic increase in spontaneous proliferation, which predominated in CD8+ lymphocytes and depended on the amount of tax mRNA. In fact, the clonal expansion of HTLV-1-positive CD8+ and CD4+ lymphocytes relied on 2 distinct mechanisms--infection prevented cell death in the former while recruiting the latter into the cell cycle. Cell cycling, but not apoptosis, depended on the level of viral-encoded tax expression. Infected tax-expressing CD4+ lymphocytes accumulated cellular defects characteristic of genetic instability. Therefore, HTLV-1 infection establishes a preleukemic phenotype that is restricted to CD4+ infected clones.

    PMID:
    16585963
    [PubMed - indexed for MEDLINE]
    PMCID:
    PMC1421359
    Free PMC Article

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