Human T-Cell Lymphotropic Virus Type 1 Infection of CD34+ Hematopoietic Progenitor Cells Induces Cell Cycle Arrest by Modulation of p21cip1/waf1 and Survivin

Authors

  • Prabal Banerjee,

    1. Department of Microbiology and Immunology, State University of New York Upstate Medical University, Syracuse, New York, USA
    2. Center for Humanized SCID Mouse Models, State University of New York Upstate Medical University, Syracuse, New York, USA
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  • Michelle Sieburg,

    1. Department of Microbiology and Immunology, State University of New York Upstate Medical University, Syracuse, New York, USA
    2. Center for Humanized SCID Mouse Models, State University of New York Upstate Medical University, Syracuse, New York, USA
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  • Elizabeth Samuelson,

    1. Department of Microbiology and Immunology, State University of New York Upstate Medical University, Syracuse, New York, USA
    2. Center for Humanized SCID Mouse Models, State University of New York Upstate Medical University, Syracuse, New York, USA
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  • Gerold Feuer

    Corresponding author
    1. Department of Microbiology and Immunology, State University of New York Upstate Medical University, Syracuse, New York, USA
    2. Center for Humanized SCID Mouse Models, State University of New York Upstate Medical University, Syracuse, New York, USA
    • Correspondence: Gerold Feuer, Ph.D., Department of Microbiology and Immunology, SUNY Upstate Medical University, 750 East Adams Street, Syracuse, New York 13210, USA. Telephone: 315-464-7681; Fax: 315-464-4417

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Errata

This article is corrected by:

  1. Errata: Human T-cell lymphotropic virus type 1 infection of CD34+ hematopoietic progenitor cells induces cell cycle arrest by modulation of p21cip1/waf1 and survivin Volume 31, Issue 9, 2031, Article first published online: September 2013

Abstract

Human T-cell lymphotropic virus type 1 (HTLV-1) is an oncogenic retrovirus and the etiologic agent of adult T-cell leukemia (ATL), an aggressive CD4+ malignancy. HTLV-2 is highly homologous to HTLV-1; however, infection with HTLV-2 has not been associated with lymphoproliferative diseases. Although HTLV-1 infection of CD4+ lymphocytes induces cellular replication and transformation, infection of CD34+ human hematopoietic progenitor cells (HPCs) strikingly results in G0/G1 cell cycle arrest and suppression of in vitro clonogenic colony formation by induction of expression of the cdk inhibitor p21cip1/waf1 (p21) and concurrent repression of survivin. Immature CD34+/CD38 hematopoietic stem cells (HSCs) were more susceptible to alterations of p21 and survivin expression as a result of HTLV-1 infection, in contrast to more mature CD34+/CD38+ HPCs. Knockdown of p21 expression in HTLV-1-infected CD34+ HPCs partially abrogated cell cycle arrest. Notably, HTLV-2, an HTLV strain that is not associated with leukemogenesis, does not significantly modulate p21 and survivin expression and does not suppress hematopoiesis from CD34+ HPCs in vitro. We speculate that the remarkable differences in the activities displayed by CD34+ HPCs following infection with HTLV-1 or HTLV-2 suggest that HTLV-1 uniquely exploits cell cycle arrest mechanisms to establish a latent infection in hematopoietic progenitor/hematopoietic stem cells and initiates preleukemic events in these cells, which eventually results in the manifestation of ATL.

Disclosure of potential conflicts of interest is found at the end of this article.

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