No evidence of murine-like gammaretroviruses in CFS patients previously identified as XMRV-infected.

Members of the gammaretroviruses--such as murine leukemia viruses (MLVs), most notably XMRV [xenotropic murine leukemia virus (X-MLV)-related virus--have been reported to be present in the blood of patients with chronic fatigue syndrome (CFS). We evaluated blood samples from 61 patients with CFS from a single clinical practice, 43 of whom had previously been identified as XMRV-positive. Our analysis included polymerase chain reaction and reverse transcription polymerase chain reaction procedures for detection of viral nucleic acids and assays for detection of infectious virus and virus-specific antibodies. We found no evidence of XMRV or other MLVs in these blood samples. In addition, we found that these gammaretroviruses were strongly (X-MLV) or partially (XMRV) susceptible to inactivation by sera from CFS patients and healthy controls, which suggested that establishment of a successful MLV infection in humans would be unlikely. Consistent with previous reports, we detected MLV sequences in commercial laboratory reagents. Our results indicate that previous evidence linking XMRV and MLVs to CFS is likely attributable to laboratory contamination.

Human herpesvirus 6 infection mimicking juvenile myelomonocytic leukemia in an infant.

In vitro cell culture studies of bone marrow and peripheral blood progenitor cells from patients with juvenile myclomonocytic leukemia (JMML) consistently show spontaneous proliferation and selective hypersensitivity to granulocyte-macrophage colony-stimulating factor (GM-CSF). This GM-CSF hypersensitivity dose-response assay has become a component of the international diagnostic criteria for JMML. The authors report a 2-week-old boy with perinatal human herpesvirus 6 (HHV-6) infection in whom in vitro bone marrow culture studies suggested the diagnosis of JMML by showing increased spontaneous proliferation, inhibition of this growth by anti-GM-CSF antibodies, and hypersensitivity to GM-CSF. Polymerase chain reaction viral studies from whole blood DNA and the shell vial viral culture assay were both positive for HHV-6. The patient's condition improved with expectant treatment, with an eventual return to normal blood counts and resolution of hepatosplenomegaly. This case of perinatal HHV-6 infection shows that viruses can initially mimic the in vitro culture results found in patients with JMML. It also illustrates that patients suspected of having JMML should be observed if there are no signs of progressive disease and concurrent features suggestive of viral infection.

Impact of human herpesvirus-6 on the frequency and severity of recurrent hepatitis C virus hepatitis in liver transplant recipients.

A role of tumor necrosis factor-alpha (TNF-alpha) In the immunopathogenesis of hepatitis C virus (HCV) infection has been proposed. The novel herpes virus, human herpes virus-6 (HHV-6), is amongst the most potent inducers of cytokines, including TNF-alpha. The impact of HHV-6 viremia on the progression of recurrent HCV hepatitis was assessed in 51 HCV-positive liver transplant recipients. The frequency of recurrent HCV hepatitis did not differ between patients with HCV viremia (47.6%, 10/21) as compared with those without HCV viremia (46.7%, 14/30, p = 0.9). However, the patients with HHV-6 viremia had a significantly higher fibrosis score upon HCV recurrence than those without HHV-6 viremia (mean 1.5 vs. 0.3, p = 0.01). An association between cytomegalovirus (CMV) viremia and HCV recurrence was not documented; 50% (15/30) of the patients with CMV viremia and 42.8% (9/21) of those without CMV viremia had recurrent HCV hepatitis (p > 0.5). Receipt of ganciclovir (administered upon the detection of CMV viremia) was associated with lower total Knodell score (mean 5.2 vs. 6.9, p = 0.05) and a trend towards lower fibrosis score (mean 0.44 vs. 1.00, p = 0.12) in patients with recurrent HCV hepatitis. Thus, HHV-6 viremia in HCV-positive liver transplant recipients identified a subgroup of patients at increased risk for early fibrosis upon HCV recurrence.