Volume 8 Supplement 1

15th International Conference on Human Retroviruses: HTLV and Related Viruses

Open Access

Development of XMRV producing B Cell lines from lymphomas from patients with Chronic Fatigue Syndrome

  • Francis Ruscetti1Email author,
  • Vincent C Lombardi2,
  • Michael Snyderman3,
  • Dan Bertolette4,
  • Kathryn S Jones1 and
  • Judy A Mikovits1
Retrovirology20118(Suppl 1):A230

DOI: 10.1186/1742-4690-8-S1-A230

Published: 6 June 2011

Previous studies have shown that CFS patients have an increased incidence of lympho-proliferative malignancy compared to the normal population [1]. While the incidence rate of non-Hodgkin’s lymphoma in the United States is 0.02%, nearly 5% of the CFS patients developed the disease. Additionally, development of cancer coincides with an outgrowth of gamma delta T cells with specific clonal T-cell receptor gamma rearrangements. We hypothesized that infection with XMRV and/or other viruses can trigger a dysregulated immune response which favors the development of B-cell lymphoma.

In a study of 300 CFS patients, 13 developed lymphoproliferative disorders. Of those tested, 11/11 were positive for XMRV and 9/9 positive for clonal TCR gamma rearrangements. Spontaneous development of four B cells lines occurred during culture of cells from CFS patients. Three developed from B cells isolated from the peripheral blood (two of whom had B cell lymphoma) and one from a bone marrow biopsy. For all four lines, the B cells have a mature CD20+, CD23+ phenotype and produce infectious XMRV at a titer of >106 infectious units/ml. Virus production occurred despite extensive hypermutation of the proviruses in these cells by APOBEC3G.. Therefore XMRV infection may accelerate the development of B cell malignancies by either indirect chronic stimulation of the immune system and/or by direct infection of the B-cell lineage . Since viral load in peripheral blood is low, these data suggest that B cells in tissues such as spleen and lymph nodes could be an in vivo reservoir for XMRV.

Authors’ Affiliations

(1)
Center for Cancer Research NCI-Frederick
(2)
Whittemore Peterson Institute, University of Nevada
(3)
Department of Medicine, State University of New York at Buffalo
(4)
Basic Research Program, SAIC-Frederick, Inc., NCI-Frederick

References

  1. Fears TR, Cummings P, Hoover RN: Cancer and a fatiguing illness in Northern Nevada: a causal hypothesis. Ann Epidemiol. 1998, 8: 245-249. 10.1016/S1047-2797(97)00203-2.View ArticlePubMedGoogle Scholar

Copyright

© Ruscetti et al; licensee BioMed Central Ltd. 2011

This article is published under license to BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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