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The HTLV-1 encoded bZIP factor promotes cell proliferation and genetic instability through activation of oncogenic microRNAs

Viruses disrupt their host cells microRNAs (miRNAs) network for facilitating their replication. That of HTLV-1 relies on the clonal expansion of its host CD4+ and CD8+ T-cells yet the virus causes adult T-cell leukemia/lymphoma (ATLL) that is regularly of the CD4+ phenotype. Infected cells express Tax and HBZ viral oncoproteins. Tax is expressed in untransformed cells where it promotes cell proliferation, genetic instability and miRNAs deregulation whereas in contrast, HBZ is expressed by untransformed and malignant T-cells where hitherto, it is considered to promote cell proliferation and to silence virus expression. Here we show that an HBZ/miRNAs axis promotes cell proliferation and genetic instability. Infected CD4+ but not CD8+ T-cells were found to overexpress oncogenic miRNAs such as miR-17 and miR-21. HBZ activated these miRNAs via a posttranscriptional mechanism while in addition to promoting cellular growth; HBZ decreased DNA stability. These effects were alleviated by either miR-21/miR-17 knockdown or by the ectopic expression of OBFC2A, a factor that protects genome stability and that we found targeted by miR-17 and miR-21 in HTLV-1 infected CD4+ T-cells. This considerably extends the oncogenic potential of HBZ and suggests that viral expression might be involved in the remarkable genetic instability of ATLL cells.

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Open Access This article is published under license to BioMed Central Ltd. This is an Open Access article is distributed under the terms of the Creative Commons Attribution License ( ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver ( ) applies to the data made available in this article, unless otherwise stated.

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Vernin, C., Pinatel, C., Gessain, A. et al. The HTLV-1 encoded bZIP factor promotes cell proliferation and genetic instability through activation of oncogenic microRNAs. Retrovirology 11, O43 (2014).

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  • Ectopic Expression
  • Clonal Expansion
  • Genome Stability
  • Genetic Instability
  • Promote Cell Proliferation