Advances in Virology

Review Article

Phylogeny-Directed Search for Murine Leukemia Virus-Like Retroviruses in Vertebrate Genomes and in Patients Suffering from Myalgic Encephalomyelitis/Chronic Fatigue Syndrome and Prostate Cancer

Table 1

How well does XMRV/HMRV fulfill the expected properties of an MLV spread to humans + means an argument for, and—an argument against expectation?


Property	Expected finding	Observed	Conclusion, for or against XMRV/HMRV in humans?

		+Hybridization array w. conserved viral 70-mers, an insensitive technique [9]. +Serendipitous.	For?
	Viral nucleic acid	+PCR (positive, XMRV [87], positive, HMRV [56] and −negative [3, 85, 88–100] results). −Proven or suspected contamination w 22Rv1-like virus and mouse DNA [3, 57, 93–96, 99–101].	Against?
	Viral nucleic acid	+Integration into host genome [8]. −Some of the integration sites occur in an XMRV-infected cell line [99].	Against?
Discovery/followup		+Cloning of XMRV into infectious clone (PC, ME/CFS) [8]. −High sequence similarity and unique recombination suggest contamination with DNA from XMRV producing cell line [2].	Against?
	Virus isolation	+Virus isolation (ME/CFS patients) [6, 102, 103]. −High sequence similarity, lack of evolution, and unique recombination suggests contamination from XMRV producing cell line [2, 82]. −Isolation results cannot be reproduced [3].	Against?
	Antiviral immune response	+SFFV FACS (ME/CFS) concordance with PCR outcome [6, 102], +ELISA (PC, ME/CFS), positive [104] and −negative [84, 92, 105–107] outcomes, −Virus neutralization, negative outcome [90], −Western blot (ME/CFS) negative outcome [105, 108], −CMIA (ME/CFS), negative outcome [109], −T-cell response, negative outcome [86].	Against?

Epidemiology, early phase	Contact with mouse	Not observed/reported	Against?

Epidemiology, late phase	Human-human spread, via saliva, sex, and mother-child	−Although occasional ME/CFS outbreaks occur, most cases are sporadic, with no spread between spouses. −No reported epidemiological link between prostate cancer and ME/CFS −No known overrepresentation in STD and in IVDU [85].	Against?

Pathogenesis	Leukemia, lymphoma	Prostate cancer?	For or against?
	Immunodeficiency	Immunodeficiency?
	Encephalitis (MAIDS)	Myalgic encephalomyelitis?
	Enteritis (MAIDS, FAIDS)	Irritable bowel syndrome?
	Autoimmunity	Thyroiditis?

Replication	Relatively easy to detect in blood	Hard to detect in blood.	Against?

Immune response	Strong B-cell response, positive WB	Weak or absent B-cell response.	Against?