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Epstein–Barr virus maintains lymphomas via its miRNAs

Oncogene volume 33, pages 1258–1264 (2014)Cite this article

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Abstract

Epstein-Barr virus (EBV) has evolved exquisite controls over its host cells, human B lymphocytes, not only directing these cells during latency to proliferate and thereby expand the pool of infected cells, but also to survive and thereby persist for the lifetime of the infected individual. Although these activities ensure the virus is successful, they also make the virus oncogenic, particularly when infected people are immunosuppressed. Here we show, strikingly, that one set of EBV’s microRNAs (miRNAs) both sustain Burkitt’s lymphoma (BL) cells in the absence of other viral oncogenes and promote the transformation of primary B lymphocytes. BL cells were engineered to lose EBV and found to die by apoptosis and could be rescued by constitutively expressing viral miRNAs in them. Two of these EBV miRNAs were found to target caspase 3 to inhibit apoptosis at physiological concentrations.

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Acknowledgements

We thank Alan Rickinson for kindly providing the early passage BL cell lines and Dagmar Pich for her invaluable support. This work was funded by grants from the National Cancer Institute, National Institutes of Health (grant P01 CA022443, grants R01 CA133027 and R01 CA070723) and Deutsche Forschungsgemeinschaft (grants SFB455 and SFBTR5). David Vereide was supported by a predoctoral fellowship from the National Cancer Center. Takanobu Tagawa is supported by a predoctoral grant of DAAD, German Academic Exchange Service. Bill Sugden is an American Cancer Society Research Professor.

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Authors and Affiliations

  1. McArdle Laboratory for Cancer Research, University of Wisconsin—Madison, Madison, WI, USA

    D T Vereide, Y-F Chiu, M Hayes & B Sugden

  2. Research Unit Gene Vectors, DZIF German Centre for Infection Research, Munich, Munich, Germany

    E Seto, T Tagawa & W Hammerschmidt

  3. Helmholtz Zentrum München, German Research Center for Environmental Health, Munich, Germany

    E Seto, T Tagawa & W Hammerschmidt

  4. Heinrich-Pette-Institute, Leibniz Institute for Experimental Virology, Hamburg, Germany

    A Grundhoff

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  1. D T Vereide
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  2. E Seto
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  3. Y-F Chiu
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  4. M Hayes
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  5. T Tagawa
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  6. A Grundhoff
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  7. W Hammerschmidt
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  8. B Sugden
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Correspondence to B Sugden.

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Vereide, D., Seto, E., Chiu, YF. et al. Epstein–Barr virus maintains lymphomas via its miRNAs. Oncogene 33, 1258–1264 (2014). https://doi.org/10.1038/onc.2013.71

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