Possible widespread low-level occurrence of murine leukemia virus-related gene sequences in humans

Abstract

The article by Lo and colleagues (1) is widely reported as a confirmation of the earlier report of Lombardi et al. (2). In fact, there are major differences, including the inability to detect xenotropic murine leukemia virus-related virus in their patient cohort, but rather finding evidence for polytropic murine endogenous γ-retroviruses. More significant is the clear difference between the absence, except in one patient with chronic fatigue syndrome (CFS), of virus envelope sequences in the publication of Lo et al. (1), versus a finding of envelope sequences in 7 of 11 tested patients with CFS in the study of Lombardi et al. (2). The results are also presented as a true qualitative distinction between CFS patients and healthy controls. The use of the nested PCR at near the limits of its sensitivity, however, does not exclude a lower than detectable level of mouse endogenous retroviruses in many healthy individuals. The numerous “nonspecific” bands generated in the nested PCR assays on control and patient samples, as reported by Lo et al. (1), mean that any retroviral sequences would need to compete for primers with the nonspecific reactions occurring with normal DNA. The primer cross-reactivity with DNA sequences other than those of murine retroviruses limits the possible detection of authentic murine retroviral sequences potentially present in DNA of healthy controls. Quantitative increases in the levels of various microbes are characteristic of many CFS cases, and this may also apply to murine retroviruses. It is noteworthy that the electrophoresis data illustrated on the control and patient samples (figures 1B and 2B in ref. 1) were obtained using different nested primers. The authors may wish to comment on whether the patterns of nonspecific bandings were essentially identical in the patients versus the control samples using the same secondary sets of nested primers. Filtering of plasma before ultracentrifugation of plasma would help eliminate the possibility of viral RNA being present in cellular debris rather than as cell-free virus particles. Finally, in concluding an association of murine retroviruses and CFS, it would have been preferable to test matched controls from the same geographic area as the CFS patients and to include patients with non-CFS-related chronic illnesses.