Blomberg J, Sheikholvaezin A, Elfaitouri A, Blomberg F, Sjösten A, Ulfstedt JM, Pipkorn R, Källander C, Öhrmalm C, Sperber G
Section of Clinical Microbiology, Department of Medical Sciences, Uppsala University, Uppsala, Sweden
Gammaretrovirus-like sequences occur in most vertebrate genomes. Murine Leukemia Virus (MLV) like retroviruses (MLLVs) are a subset, which may be pathogenic and spread cross-species. Retroviruses highly similar to MLLVs (xenotropic murine retrovirus related virus (XMRV) and Human Mouse retrovirus-like RetroViruses (HMRVs)) reported from patients suffering from prostate cancer (PC) and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) raise the possibility that also humans have been infected. Structurally intact, potentially infectious MLLVs occur in the genomes of some mammals, especially mouse. Mouse MLLVs contain three major groups. One, MERV G3, contained MLVs and XMRV/HMRV. Its presence in mouse DNA, and the abundance of xenotropic MLVs in biologicals, is a source of false positivity. Theoretically, XMRV/HMRV could be one of several MLLV transspecies infections. MLLV pathobiology and diversity indicate optimal strategies for investigating XMRV/HMRV in humans and raise ethical concerns. The alternatives that XMRV/HMRV may give a hard-to-detect “stealth” infection, or that XMRV/HMRV never reached humans, have to be considered.
Comment by ME Research UK
Professor Blomberg, head of the Research Group of Clinical Virology at the University of Uppsala, received grant funding from ME Research UK and the Irish ME Trust to test for XMRV in Swedish patients and controls. The results of this investigation were published online in October 2011, followed by this expert review on the subject by Professor Blomberg and colleagues in a special issue of Advances in Virology.
In this complex review, Professor Blomberg explores the phylogenetics (evolutionary relatedness) of MLLVs, including their relative XMRV. He explains that the human genetic make-up also contains remnants of infections with retroviruses highly related to MLLVs, but that these were integrated into genetic make-up in the distant past. In contrast, MLLVs have repeatedly infected animals other than mice more recently; for instance, Mediterranean and middle Eastern cats, turkeys, gibbon apes, and koalas have been “invaded” by MLLVs. In infected animals, exogenous MLLVs (acquired from outside) are associated with significant diseases, such as encephalitis, malignancy (leukaemia and lymphoma), wasting, immunosuppression, and autoimmunity. This makes it especially important to establish if the human species is now also “invaded” by murine (mouse) MLLVs, such as XMRV.
Considering the accumulating number of “negative” studies unable to find XMRV/MLLVs in human populations (read a summary here), Professor Blomberg asks why XMRV might be so hard to detect. One possibility is that chronic infection could establish a low-grade infection in a limited number of cell types, with a waning immune response, becoming progressively harder to detect both by nucleic acid, virus isolation and serological methods – a phenomenon seen in experimentally XMRV-infected macaques and, apparently, not unknown in HTLV and HIV infections. Another possibility, however, is that all reports of XMRV in humans have been due to contamination or serological cross-reaction; as he says, if this were the case, “
it would be a sad outcome of a fascinating and important story”.
For a review of other recent research in this area, see our article (pdf 1.1 MB) in the Autumn 2011 issue of Breakthrough.