No evidence for XMRV in German CFS and MS patients with fatigue despite the ability of the virus to infect human blood cells in vitro

Abstract

BACKGROUND: Xenotropic murine leukemia virus-related virus (XMRV), a novel human retrovirus originally identified in prostate cancer tissues, has recently been  associated with chronic fatigue syndrome (CFS), a disabling disease of unknown  etiology affecting millions of people worldwide. However, several subsequent  studies failed to detect the virus in patients suffering from these illnesses or  in healthy subjects. Here we report the results of efforts to detect antibody  responses and viral sequences in samples from a cohort of German CFS and  relapsing remitting multiple sclerosis (MS) patients with fatigue symptoms.  METHODOLOGY: Blood samples were taken from a cohort of 39 patients fulfilling the  Fukuda/CDC criteria (CFS), from 112 patients with an established MS diagnosis and  from 40 healthy donors. Fatigue severity in MS patients was assessed using the  Fatigue Severity Scale (FSS). Validated Gag- and Env-ELISA assays were used to  screen sera for XMRV antibodies. PHA-activated PBMC were cultured for seven days  in the presence of IL-2 and DNA isolated from these cultures as well as from  co-cultures of PBMC and highly permissive LNCaP cells was analyzed by nested PCR  for the presence of the XMRV gag gene. In addition, PBMC cultures were exposed to  22Rv1-derived XMRV to assess infectivity and virus production. CONCLUSION: None  of the screened sera from CFS and MS patients or healthy blood donors tested  positive for XMRV specific antibodies and all PBMC (and PBMC plus LNCaP) cultures  remained negative for XMRV sequences by nested PCR. These results argue against  an association between XMRV infection and CFS and MS in Germany. However, we  could confirm that PBMC cultures from healthy donors and from CFS patients can be  experimentally infected by XMRV, resulting in the release of low levels of  transmittable virus.