title: Xenotropic murine leukemia virus-related virus is not associated with chronic fatigue syndrome in patients from different areas of the us in the 1990s.
abstract: BACKGROUND
  In 2009, xenotropic murine leukemia virus-related virus (XMRV) was reported in 67% of patients with chronic fatigue syndrome (CFS) compared to 4% of controls. Since then numerous reports failed to detect XMRV in other cohorts of CFS patients, and some studies suggested that XMRV sequences in human samples might be due to contamination of these samples with mouse DNA.
  
  
  RESULTS
  We determined the prevalence of XMRV in patients with CFS from similar areas in the United States as the original 2009 study, along with patients with chronic inflammatory disorders and healthy persons. Using quantitative PCR, we initially detected very low level signals for XMRV DNA in 15% of patients with CFS; however, the frequency of PCR positivity was no different between patients with CFS and controls. Repeated attempts to isolate PCR products from these reactions were unsuccessful. These findings were supported by our observations that PHA and IL-2 stimulation of peripheral blood mononuclear cells from patients with apparently low levels of XMRV, which induced virus replication in the 2009 report, resulted in the disappearance of the signal for XMRV DNA in the cells. Immunoprecipitation of XMRV-infected cell lysates using serum from patients from whom we initially detected low levels of XMRV DNA followed by immunoblotting with antibodies to XMRV gp70 protein failed to detect antibody in the patients, although one control had a weak level of reactivity. Diverse murine leukemia virus (MLV) sequences were obtained by nested PCR with a similar frequency in CFS patients and controls. Finally, we did not detect XMRV sequences in patients with several chronic inflammatory disorders including rheumatoid arthritis, Bechet's disease, and systemic lupus erythematosus.
  
  
  CONCLUSIONS
  We found no definitive evidence for XMRV DNA sequences or antibody in our cohort of CFS patients, which like the original 2009 study, included patients from diverse regions of the United States. In addition, XMRV was not detected in a cohort of patients with chronic inflammatory disorders.
authors.affiliation: Medical Virology Section, Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Mir A
authors.initials: MA
authors.lastname: Ali
authors.forename: Janet K
authors.initials: JK
authors.lastname: Dale
authors.forename: Christine A
authors.initials: CA
authors.lastname: Kozak
authors.forename: Raphaela
authors.initials: R
authors.lastname: Goldbach-Mansky
authors.forename: Frederick W
authors.initials: FW
authors.lastname: Miller
authors.forename: Stephen E
authors.initials: SE
authors.lastname: Straus
authors.forename: Jeffrey I
authors.initials: JI
authors.lastname: Cohen
mesh_terms: D000914:Antibodies, Viral / Q000097:blood*; D001769:Blood / Q000821:virology*; D015673:Fatigue Syndrome, Chronic / Q000209:etiology / Q000821:virology*; D006801:Humans; D015151:Immunoblotting; D015995:Prevalence; D060888:Real-Time Polymerase Chain Reaction; D012192:Retroviridae Infections / Q000150:complications* / Q000821:virology; D014481:United States; D058008:Xenotropic murine leukemia virus-related virus / Q000302:isolation & purification* / Q000472:pathogenicity*
chemical_list: D000914:Antibodies, Viral