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Research Article

Detection of MLV-related virus gene sequences in blood of patients with chronic fatigue syndrome and healthy blood donors

Shyh-Ching Lo, Natalia Pripuzova, Bingjie Li, Anthony L. Komaroff, Guo-Chiuan Hung, Richard Wang, and Harvey J. Alter
  1. aTissue Microbiology Laboratory, Division of Cellular and Gene Therapies and Division of Human Tissues, Office of Cellular, Tissue and Gene Therapy, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, MD 20892;
  2. bDepartment of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115; and
  3. cDepartment of Transfusion Medicine, The Warren Grant Magnuson Clinical Center, National Institutes of Health, Bethesda, MD 20892

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PNAS first published August 23, 2010; https://doi.org/10.1073/pnas.1006901107
Shyh-Ching Lo
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  • For correspondence: shyhching.lo@FDA.hhs.gov halter@mail.nih.gov
Natalia Pripuzova
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Bingjie Li
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Anthony L. Komaroff
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Guo-Chiuan Hung
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Richard Wang
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Harvey J. Alter
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  • For correspondence: shyhching.lo@FDA.hhs.gov halter@mail.nih.gov
  1. Contributed by Harvey J. Alter, May 25, 2010 (sent for review March 23, 2010)

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Abstract

Chronic fatigue syndrome (CFS) is a serious systemic illness of unknown cause. A recent study identified DNA from a xenotropic murine leukemia virus-related virus (XMRV) in peripheral blood mononuclear cells (PBMCs) from 68 of 101 patients (67%) by nested PCR, as compared with 8 of 218 (3.7%) healthy controls. However, four subsequent reports failed to detect any murine leukemia virus (MLV)-related virus gene sequences in blood of CFS patients. We examined 41 PBMC-derived DNA samples from 37 patients meeting accepted diagnostic criteria for CFS and found MLV-like virus gag gene sequences in 32 of 37 (86.5%) compared with only 3 of 44 (6.8%) healthy volunteer blood donors. No evidence of mouse DNA contamination was detected in the PCR assay system or the clinical samples. Seven of 8 gag-positive patients tested again positive in a sample obtained nearly 15 y later. In contrast to the reported findings of near-genetic identity of all XMRVs, we identified a genetically diverse group of MLV-related viruses. The gag and env sequences from CFS patients were more closely related to those of polytropic mouse endogenous retroviruses than to those of XMRVs and were even less closely related to those of ecotropic MLVs. Further studies are needed to determine whether the same strong association with MLV-related viruses is found in other groups of patients with CFS, whether these viruses play a causative role in the development of CFS, and whether they represent a threat to the blood supply.

  • xenotropic murine leukemia virus-related virus
  • murine leukemia virus-like virus
  • viral gag gene sequence
  • polytropic
  • mouse mitochondria DNA PCR

Footnotes

  • 1To whom correspondence may be addressed. E-mail: shyhching.lo{at}FDA.hhs.gov or halter{at}mail.nih.gov.
  • Author contributions: S.-C.L., N.P., and B.L. designed research; G.-C.H. designed mouse-specific mitochondria PCR assay; N.P. and B.L. performed research; B.L. and R.W. contributed new reagents/analytic tools; S.-C.L., N.P., G.-C.H., and R.W. analyzed data; and S.-C.L., N.P., A.L.K., and H.J.A. wrote the paper.

  • The authors declare no conflict of interest.

  • This article contains supporting information online at www.pnas.org/lookup/suppl/doi:10.1073/pnas.1006901107/-/DCSupplemental.

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    Detection of MLV-related virus gene sequences in blood of patients with chronic fatigue syndrome and healthy blood donors
    Shyh-Ching Lo, Natalia Pripuzova, Bingjie Li, Anthony L. Komaroff, Guo-Chiuan Hung, Richard Wang, Harvey J. Alter
    Proceedings of the National Academy of Sciences Aug 2010, 201006901; DOI: 10.1073/pnas.1006901107

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    Detection of MLV-related virus gene sequences in blood of patients with chronic fatigue syndrome and healthy blood donors
    Shyh-Ching Lo, Natalia Pripuzova, Bingjie Li, Anthony L. Komaroff, Guo-Chiuan Hung, Richard Wang, Harvey J. Alter
    Proceedings of the National Academy of Sciences Aug 2010, 201006901; DOI: 10.1073/pnas.1006901107
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