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Tumor outgrowth in peripheral blood mononuclear cell-injected SCID mice is not associated with early Epstein–Barr virus reactivation

Leukemia volume 17, pages 1643–1649 (2003)Cite this article

Abstract

Epstein–Barr virus (EBV)-positive B-cell lymphoproliferative disease develops in severe combined immunodeficient (SCID) mice inoculated with peripheral blood mononuclear cells (PBMC) from EBV+ individuals (SCID/hu mice). In this study, we investigated the contribution of EBV reactivation and de novo infection of B lymphocytes to tumor outgrowth in SCID/hu mice. Evaluation of BZLF-1, an early EBV activation transcript, in cells recovered from the mouse peritoneal cavity within 16 days following PBMC transfer did not reveal EBV reactivation, while BZLF-1 expression was only detected in tumor masses or in vitro established lymphoblastoid cell lines. To confirm these data by a different strategy, we coinjected PBMC from seropositive donors with purified B cells from seronegative donors of different sex. Fluorescence in situ hydridization analysis of the resulting tumor masses disclosed that the overwhelming majority of lymphoma cells originated from the seropositive donor, implying that no substantial in vivo production and transmission of virus had occurred. Further, treatment of SCID/hu mice with ganciclovir did not prevent lymphoma development. Our results suggest that in the SCID/hu mouse, early EBV replication and secondary infection of bystander B cells does not occur, and that the direct outgrowth of the transformed B lymphocytes present within the PBMC inoculum is the predominant mechanism, which leads to lymphoma generation in this experimental model.

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Acknowledgements

We are indebted to Drs G De Silvestro and P Marson of the Blood Transfusion Unit for precious help in lymphapheresis procedures. We are also grateful to Dr W Habeler for help with animal procedures and P Gallo for the artwork. This work was supported in part by grants from the Italian Association for Research on Cancer (AIRC), Italian Federation for Research on Cancer (FIRC), Ministry of Health (ISS, AIDS Project), MIUR 40%, 60%, and FIRB.

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Authors and Affiliations

  1. Department of Oncology and Surgical Sciences, University of Padova, Padova, Italy

    E Piovan, L Bonaldi, S Indraccolo, V Tosello, C Menin, L Chieco-Bianchi & A Amadori

  2. Molecular Oncology and Cytodiagnostic Unit, Azienda Ospedaliera di Padova, Padova, Italy

    L Bonaldi

  3. IST-Viral and Molecular Oncology Section, Padova, Italy

    S Indraccolo & C Menin

  4. ENT Department, University of Padova, Padova, Italy

    F Comacchio

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Piovan, E., Bonaldi, L., Indraccolo, S. et al. Tumor outgrowth in peripheral blood mononuclear cell-injected SCID mice is not associated with early Epstein–Barr virus reactivation. Leukemia 17, 1643–1649 (2003). https://doi.org/10.1038/sj.leu.2403005

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