Abstract

BackgroundXenotropic murine leukemia virus-related virus (XMRV) has been found in the prostatic tissue of prostate cancer patients and in the blood of chronic fatigue syndrome patients. However, numerous studies have found little to no trace of XMRV in different human cohorts. Based on evidence suggesting common transmission routes between XMRV and HIV-1, HIV-1 infected individuals may represent a high-risk group for XMRV infection and spread.Methodology/Principal FindingsDNA was isolated from the peripheral blood mononuclear cells (PBMCs) of 179 HIV-1 infected treatment naïve patients, 86 of which were coinfected with HCV, and 54 healthy blood donors. DNA was screened for XMRV provirus with two sensitive, published PCR assays targeting XMRV gag and env and one sensitive, published nested PCR assay targeting env. Detection of XMRV was confirmed by DNA sequencing. One of the 179 HIV-1 infected patients tested positive for gag by non-nested PCR whereas the two other assays did not detect XMRV in any specimen. All healthy blood donors were negative for XMRV proviral sequences. Sera from 23 HIV-1 infected patients (15 HCV+) and 12 healthy donors were screened for the presence of XMRV-reactive antibodies by Western blot. Thirteen sera (57%) from HIV-1+ patients and 6 sera (50%) from healthy donors showed reactivity to XMRV-infected cell lysate.Conclusions/SignificanceThe virtual absence of XMRV in PBMCs suggests that XMRV is not associated with HIV-1 infected or HIV-1/HCV coinfected patients, or blood donors. Although we noted isolated incidents of serum reactivity to XMRV, we are unable to verify the antibodies as XMRV specific.

Highlights

  • Xenotropic murine leukemia virus-related virus (XMRV) is a gammaretrovirus first discovered in the cancer-associated stroma of prostate cancer patients in 2006 [1]

  • In order to maximize the probability of detecting XMRV by polymerase chain reaction (PCR) in patient specimens that harbor provirus, we decided to use three different published assays that have been successful in earlier studies (Table 1)

  • Two non-nested primer sets developed by Lombardi et al were shown to be capable of detecting XMRV gag and env in the peripheral blood mononuclear cells (PBMCs) of chronic fatigue syndrome patients, whereas a nested PCR assay developed in our laboratory had been used to detect XMRV env in the prostatic tissue of prostate cancer patients [2,36]

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Summary

Introduction

Xenotropic murine leukemia virus-related virus (XMRV) is a gammaretrovirus first discovered in the cancer-associated stroma of prostate cancer patients in 2006 [1]. XMRV DNA and infectious virions were detected in the peripheral blood mononuclear cells (PBMCs) of patients with chronic fatigue syndrome (CFS) [2]. Following these initial reports, numerous studies have either detected a very low prevalence among subjects or no XMRV at all, even in relatively large cohorts [3,4,5,6,7,8,9,10,11,12,13,14,15,16]. Based on evidence suggesting common transmission routes between XMRV and HIV-1, HIV-1 infected individuals may represent a high-risk group for XMRV infection and spread

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