Human T-cell lymphotropic virus type 1 infection of CD34+ hematopoietic progenitor cells induces cell cycle arrest by modulation of p21(cip1/waf1) and survivin
| Autor: | Prabal Banerjee, Gerold Feuer, Michelle Sieburg, Elizabeth Samuelson |
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| Rok vydání: | 2008 |
| Předmět: |
Cyclin-Dependent Kinase Inhibitor p21
Cell cycle checkpoint viruses Survivin CD34 Antigens CD34 CD38 Biology Transfection Cell Line Inhibitor of Apoptosis Proteins Viral Envelope Proteins immune system diseases hemic and lymphatic diseases Humans Human T cell lymphotropic virus type 1 Human T-lymphotropic virus 1 Membrane Glycoproteins Genes pX Cell Cycle Lentivirus Cell Biology Cell cycle Hematopoietic Stem Cells Virology HTLV-I Infections Lymphoproliferative Disorders Gene Expression Regulation Neoplastic Haematopoiesis Cancer research Molecular Medicine Stem cell Microtubule-Associated Proteins Developmental Biology |
| Zdroj: | Stem cells (Dayton, Ohio). 26(12) |
| ISSN: | 1549-4918 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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