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Coclusion
Research on XMRV/HMRV in humans is evolving rapidly. There is a great need for confirmation of the reports on XMRV/HMRVs in PC and ME/CFS. In view of the recently demonstrated diversity of retroviral sequences in ME/CFS, it is also important to establish the detection range of XMRV/HMRV detection methods. Contamination of cell cultures with 22Rv1 virus and PCRs with MLV nucleic acid and mouse DNA is known to occur. Whether all reports on MLLVs in humans can be explained by them is uncertain, but not unlikely. The XMRV/HMRV story has both credible and less credible aspects (Table 1). The original XMRV detection in prostate cancer was serendipitous and made with several independent techniques, together forming a credible case. The proven integration into human DNA was especially convincing. The finding of XMRV/HMRV in ME/CFS also has a credible aspect; the immunomodulating properties of MLLVs could theoretically explain the disease. However, the epidemiology of XMRV/HMRV transmission still is unclear. The absence of an easily measurable immune response is also a memento.
We conclude that MLLVs are widespread as ERVs among vertebrates. There are many signs of interspecies transmission of MLLVs. However, only a few of the MLLVs are structurally intact. The mouse genome is unique in its high content of MLLVs. It contains three major MLLV groups, of which two (G1 and G2) have not hitherto been reported. Group G3 contains the MLVs and all or nearly all of the MLV-like retroviruses which have so far been detected in humans, that is, XMRV and HMRV.
The study of XMRV/HMRV is important from a range of perspectives, one of which is screening of blood donors for potentially harmful pathogens. Xenotropic viruses also raise concerns regarding research into xenotransplantation of organs [16].
The detection of human infection with XMRV/HMRV has proven to be difficult. This may either be due to absence of the virus or to a low-grade infection, with a minimal viral replication and a minimal serological response. Although that goes contrary to expectations, such a situation sometimes occurs in HTLV and HIV infections.
