No evidence of XMRV in prostate cancer cohorts in the Midwestern United States

<p>Abstract</p> <p>Background</p> <p>Xenotropic murine leukemia virus (MLV)-related virus (XMRV) was initially identified in prostate cancer (PCa) tissue, particularly in the prostatic stromal fibroblasts, of patients homozygous for the RNASEL R462Q mutation. A subseque...

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Main Authors: Ohmine Seiga, Thatava Tayaramma, Blackburn Patrick R, Tonne Jason M, Squillace Karen A, Hué Stéphane, Sakuma Toshie, Towers Greg J, Ikeda Yasuhiro
Format: Article
Language:English
Published: BMC 2011-03-01
Series:Retrovirology
Online Access:http://www.retrovirology.com/content/8/1/23
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author Ohmine Seiga
Thatava Tayaramma
Blackburn Patrick R
Tonne Jason M
Squillace Karen A
Hué Stéphane
Sakuma Toshie
Towers Greg J
Ikeda Yasuhiro
author_facet Ohmine Seiga
Thatava Tayaramma
Blackburn Patrick R
Tonne Jason M
Squillace Karen A
Hué Stéphane
Sakuma Toshie
Towers Greg J
Ikeda Yasuhiro
author_sort Ohmine Seiga
collection DOAJ
description <p>Abstract</p> <p>Background</p> <p>Xenotropic murine leukemia virus (MLV)-related virus (XMRV) was initially identified in prostate cancer (PCa) tissue, particularly in the prostatic stromal fibroblasts, of patients homozygous for the RNASEL R462Q mutation. A subsequent study reported XMRV antigens in malignant prostatic epithelium and association of XMRV infection with PCa, especially higher-grade tumors, independently of the RNASEL polymorphism. Further studies showed high prevalence of XMRV or related MLV sequences in chronic fatigue syndrome patients (CFS), while others found no, or low, prevalence of XMRV in a variety of diseases including PCa or CFS. Thus, the etiological link between XMRV and human disease remains elusive. To address the association between XMRV infection and PCa, we have tested prostate tissues and human sera for the presence of viral DNA, viral antigens and anti-XMRV antibodies.</p> <p>Results</p> <p>Real-time PCR analysis of 110 PCa (Gleason scores >4) and 40 benign and normal prostate tissues identified six positive samples (5 PCa and 1 non-PCa). No statistical link was observed between the presence of proviral DNA and PCa, PCa grades, and the <it>RNASEL </it>R462Q mutation. The amplified viral sequences were distantly related to XMRV, but nearly identical to endogenous MLV sequences in mice. The PCR positive samples were also positive for mouse mitochondrial DNA by nested PCR, suggesting contamination of the samples with mouse DNA. Immuno-histochemistry (IHC) with an anti-XMRV antibody, but not an anti-MLV antibody that recognizes XMRV, sporadically identified antigen-positive cells in prostatic epithelium, irrespectively of the status of viral DNA detection. No serum (159 PCa and 201 age-matched controls) showed strong neutralization of XMRV infection at 1:10 dilution.</p> <p>Conclusion</p> <p>The lack of XMRV sequences or strong anti-XMRV neutralizing antibodies indicates no or very low prevalence of XMRV in our cohorts. We conclude that real-time PCR- and IHC-positive samples were due to laboratory contamination and non-specific immune reactions, respectively.</p>
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spelling doaj.art-c9fb5ecaa2f646e9bfbf622c9da879622022-12-22T02:08:59ZengBMCRetrovirology1742-46902011-03-01812310.1186/1742-4690-8-23No evidence of XMRV in prostate cancer cohorts in the Midwestern United StatesOhmine SeigaThatava TayarammaBlackburn Patrick RTonne Jason MSquillace Karen AHué StéphaneSakuma ToshieTowers Greg JIkeda Yasuhiro<p>Abstract</p> <p>Background</p> <p>Xenotropic murine leukemia virus (MLV)-related virus (XMRV) was initially identified in prostate cancer (PCa) tissue, particularly in the prostatic stromal fibroblasts, of patients homozygous for the RNASEL R462Q mutation. A subsequent study reported XMRV antigens in malignant prostatic epithelium and association of XMRV infection with PCa, especially higher-grade tumors, independently of the RNASEL polymorphism. Further studies showed high prevalence of XMRV or related MLV sequences in chronic fatigue syndrome patients (CFS), while others found no, or low, prevalence of XMRV in a variety of diseases including PCa or CFS. Thus, the etiological link between XMRV and human disease remains elusive. To address the association between XMRV infection and PCa, we have tested prostate tissues and human sera for the presence of viral DNA, viral antigens and anti-XMRV antibodies.</p> <p>Results</p> <p>Real-time PCR analysis of 110 PCa (Gleason scores >4) and 40 benign and normal prostate tissues identified six positive samples (5 PCa and 1 non-PCa). No statistical link was observed between the presence of proviral DNA and PCa, PCa grades, and the <it>RNASEL </it>R462Q mutation. The amplified viral sequences were distantly related to XMRV, but nearly identical to endogenous MLV sequences in mice. The PCR positive samples were also positive for mouse mitochondrial DNA by nested PCR, suggesting contamination of the samples with mouse DNA. Immuno-histochemistry (IHC) with an anti-XMRV antibody, but not an anti-MLV antibody that recognizes XMRV, sporadically identified antigen-positive cells in prostatic epithelium, irrespectively of the status of viral DNA detection. No serum (159 PCa and 201 age-matched controls) showed strong neutralization of XMRV infection at 1:10 dilution.</p> <p>Conclusion</p> <p>The lack of XMRV sequences or strong anti-XMRV neutralizing antibodies indicates no or very low prevalence of XMRV in our cohorts. We conclude that real-time PCR- and IHC-positive samples were due to laboratory contamination and non-specific immune reactions, respectively.</p>http://www.retrovirology.com/content/8/1/23
spellingShingle Ohmine Seiga
Thatava Tayaramma
Blackburn Patrick R
Tonne Jason M
Squillace Karen A
Hué Stéphane
Sakuma Toshie
Towers Greg J
Ikeda Yasuhiro
No evidence of XMRV in prostate cancer cohorts in the Midwestern United States
Retrovirology
title No evidence of XMRV in prostate cancer cohorts in the Midwestern United States
title_full No evidence of XMRV in prostate cancer cohorts in the Midwestern United States
title_fullStr No evidence of XMRV in prostate cancer cohorts in the Midwestern United States
title_full_unstemmed No evidence of XMRV in prostate cancer cohorts in the Midwestern United States
title_short No evidence of XMRV in prostate cancer cohorts in the Midwestern United States
title_sort no evidence of xmrv in prostate cancer cohorts in the midwestern united states
url http://www.retrovirology.com/content/8/1/23
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