Abstract

BackgroundThe recent report of gammaretroviruses of probable murine origin in humans, called xenotropic murine retrovirus related virus (XMRV) and human murine leukemia virus related virus (HMRV), necessitated a bioinformatic search for this virus in genomes of the mouse and other vertebrates, and by PCR in humans.ResultsThree major groups of murine endogenous gammaretroviruses were identified. The third group encompassed both exogenous and endogenous Murine Leukemia Viruses (MLVs), and most XMRV/HMRV sequences reported from patients suffering from myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Two sensitive real-time PCRs for this group were developed. The predicted and observed amplification range for these and three published XMRV/HMRV PCRs demonstrated conspicuous differences between some of them, partly explainable by a recombinatorial origin of XMRV. Three reverse transcription real-time PCRs (RTQPCRs), directed against conserved and not overlapping stretches of env, gag and integrase (INT) sequences of XMRV/HMRV were used on human samples. White blood cells from 78 patients suffering from ME/CFS, of which 30 patients also fulfilled the diagnostic criteria for fibromyalgia (ME/CFS/FM) and in 7 patients with fibromyalgia (FM) only, all from the Gothenburg area of Sweden. As controls we analyzed 168 sera from Uppsala blood donors. We controlled for presence and amplifiability of nucleic acid and for mouse DNA contamination. To score as positive, a sample had to react with several of the XMRV/HMRV PCRs. None of the samples gave PCR reactions which fulfilled the positivity criteria.ConclusionsXMRV/HMRV like proviruses occur in the third murine gammaretrovirus group, characterized here. PCRs developed by us, and others, approximately cover this group, except for the INT RTQPCR, which is rather strictly XMRV specific. Using such PCRs, XMRV/HMRV could not be detected in PBMC and plasma samples from Swedish patients suffering from ME/CFS/FM, and in sera from Swedish blood donors.

Highlights

  • A gammaretrovirus related to the Mouse Leukemia Viruses (MLVs), was 2006 found in a few percent of patients suffering from prostate cancer [1]

  • In 2010, the term xenotropic murine retrovirus related virus (XMRV) was complemented with ‘‘human murine leukemia virus related virus (HMRV)’’ (Human retrovirus related to Murine RetroVirus), because gammaretroviral sequences found in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) were more diverse than just XMRV [3]

  • It is known that endogenous retroviral sequences (ERVs) highly related to XMRV and HMRV occur in the mouse genome

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Summary

Introduction

A gammaretrovirus related to the Mouse Leukemia Viruses (MLVs), was 2006 found in a few percent of patients suffering from prostate cancer [1]. It was initially named XMRV, ‘‘Xenotropic Murine retrovirus Related Virus’’. We will in the following refer to the gammaretroviruses related to murine ERVs which have been reported to occur in humans as ‘‘XMRV/HMRV’’ It is unknown if XMRV/HMRV is confined to the mouse genome. The recent report of gammaretroviruses of probable murine origin in humans, called xenotropic murine retrovirus related virus (XMRV) and human murine leukemia virus related virus (HMRV), necessitated a bioinformatic search for this virus in genomes of the mouse and other vertebrates, and by PCR in humans

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