Date Published: June 9, 2011
Publisher: Hindawi Publishing Corporation
Author(s): Mark James Robinson, Philip William Tuke, Otto Erlwein, Kate I. Tettmar, Steve Kaye, Kikkeri N. Naresh, Anup Patel, Marjorie M. Walker, Takahiro Kimura, Ganesh Gopalakrishnan, Richard S. Tedder, Myra O. McClure.
Xenotropic murine leukaemia virus-related virus (XMRV) is a recently described retrovirus which has been claimed to infect humans and cause associated pathology. Initially identified in the US in patients with prostate cancer and subsequently in patients with chronic fatigue syndrome, doubt now exists that XMRV is a human pathogen. We studied the prevalence of genetic sequences of XMRV and related MuLV sequences in human prostate cancer, from B cell lymphoma patients and from UK blood donors. Nucleic acid was extracted from fresh prostate tissue biopsies, formalin-fixed paraffin-embedded (FFPE) prostate tissue and FFPE B-cell lymphoma. The presence of XMRV-specific LTR or MuLV generic gag-like sequences was investigated by nested PCR. To control for mouse DNA contamination, a PCR that detected intracisternal A-type particle (IAP) sequences was included. In addition, DNA and RNA were extracted from whole blood taken from UK blood donors and screened for XMRV sequences by real-time PCR. XMRV or MuLV-like sequences were not amplified from tissue samples. Occasionally MuLV gag and XMRV-LTR sequences were amplified from Indian prostate cancer samples, but were always detected in conjunction with contaminating murine genomic DNA. We found no evidence of XMRV or MuLV infection in the UK blood donors.
In 2006, a new gammaretrovirus, xenotropic murine leukaemia virus-related virus (XMRV), was discovered by the Virochip analysis in prostate cancer tissue from patients homozygous for an RNase L mutation . In these patients, the innate antiviral defence RNase L pathway is defective; hence, these patients are likely to be susceptible to viral infection and a population more likely to find a novel virus with disease association in. When a second US study found that 6% of all prostate cancer patients, independent of RNase L mutations, were infected with the virus, thus broadening the population at risk , interest in XMRV intensified. However, subsequent studies from the USA [3, 4] and all European studies [5–7] failed to confirm the presence of XMRV in prostate tissue. More recently it has been suggested that XMRV detection in prostate tissue in the US could be related to the specificity and conditions of the PCR used .
Using highly sensitive PCRs with primers that detect XMRV and primers that detect MuLV-like sequences, no proviral DNA was detected in any of the prostate cancer samples independently of murine DNA contamination. This served to confirm our previous studies in which FFPE prostate tissue was tested and XMRV/MuLV sequences failed to be amplified . Here we have added further data to show that no XMRV or MuLV-like sequences can be detected in fresh UK prostate tissue or in prostate cancer samples collected from Japan. Samples from India showed evidence of MuLV and XMRV sequences when viral genomic sequences were amplified by nested PCR. However, this was concordant with murine genomic DNA contamination detected using primers to IAP. IAPs are retrotransposons present at the level of around 1000 copies per mouse genome . Thus, IAP PCR represents a highly sensitive detection method for murine DNA. Although the sample size was small (n = 10), we found no evidence to suggest that XMRV might be involved in other cancers, such as diffuse large B-cell lymphoma.
The authors declare no conflict of interests.