XMRV and prostate cancer—a 'final' perspective

Sfanos, Karen S.; Aloia, Amanda L.; Marzo, Angelo M. De; Rein, Alan

doi:10.1038/nrurol.2011.225

Cited by 19 publications

(13 citation statements)

References 66 publications

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“…In contrast, in other studies have been found very low or no XMRV prevalence in prostate cancers in Europe (Germany, and the Netherlands) and USA using only RT-PCR (Fischer et al, 2008;Hohn et al, 2009;Aloia et al, 2010;Silverman et al, 2010;Sakuma et al, 2011;Sfanos, 2011;Stieler et al, 2011). Moreover other findings imply that XMRV does not present in humans, and is only seen in the laboratory contamination (Sfanos et al, 2012). Thus, the role of XMRV in human pathogenesis is controversial (Switzer et al, 2011).…”

Section: Introductionmentioning

confidence: 93%

No Detection of Xenotropic Murine Leukemia Virus-Related Viruses in Prostate Cancer in Sanandaj, West of Iran

Khodabandehloo

Hosseini²,

Rahmani³

et al. 2013

Asian Pacific Journal of Cancer Prevention

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Asian Pac J Cancer Prev, 14 (11), 6929-6933 IntroductionProstate cancer is the most common malignancy in men worldwide (Groom et al., 2012). The annual incidence rates of prostate cancer among Iranian population are dramatically higher than in other countries of Asia (Akbari et al., 2008). Multiple etiologies have been hypothesized for the cause of prostate cancers, including genetic defects, infectious agents and associated inflammation (Silverman et al., 2010). Identification of a potential virus as the cause of prostate cancer is very important because it could facilitate management of this disease such as treatment and prevention. A recently described retrovirus, the xenotropic murine leukemia virus-related virus (XMRV) was detected in about 40% of familial prostate cancer using a DNA microarray (Virochip) containing oligonucleotides comprising conserved sequences from known viral genomes and was strongly associated with homozygosity for the R462Q reduced activity, a variant of the antiviral enzyme, RNase L (Urisman et al., 2006).Murine leukemia viruses (MLVs) belong to gammaretroviruses in the retroviridae family, which viral RNA is reverse-transcribed to DNA during replication. They are endogenous viruses that have integrated their provirus DNA into the mouse genome and can cause leukemias, lymphomas, neurologic diseases, and has been reported to be detected in prostate cancer. However, this virus has not been detected in similar groups of patients in other studies. Herein, we sought to detect XMRV in prostate cancers and benign controls in Sanandaj, west of Iran. Materials and Methods: In a case-control study, genomic DNA was extracted from formalin fixed and paraffin embedded prostate tissues from a total of 163 Iranian patients. We developed a conventional and a nested PCR assay using primers targeting to an env specific sequence of XMRV. PCR assays were carried out on 63 prostate cancers and 100 benign prostate hyperplasias. Results: Beta-actin sequences were successfully detected in the DNA extracts from all prostate tissues, confirming DNA extraction integrity. We did not detect XMRV in samples either from prostate cancers or benign prostate hyperplasias using XMRV specific primers. Conclusions: We conclude that in our population XMRV does not play a role in genesis of prostate cancer.

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Section: Introductionmentioning

confidence: 93%

No Detection of Xenotropic Murine Leukemia Virus-Related Viruses in Prostate Cancer in Sanandaj, West of Iran

Khodabandehloo

Hosseini²,

Rahmani³

et al. 2013

Asian Pacific Journal of Cancer Prevention

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“…Several follow-up studies, however, did not detect XMRV in PCa patient samples (Fischer et al, 2008; Sfanos et al, 2008; Hohn et al, 2009; Aloia et al, 2010; Sakuma et al, 2011; Switzer et al, 2011). In addition, studies conducted in 2009 (Schlaberg et al, 2009) and 2010 (Arnold et al, 2010; Danielson et al, 2010) supporting the presence of XMRV in PCa had apparent contradictions to the original report as well as to each other, including discrepancies in the presence of virus in tumor versus benign tissues and discordance in cellular localization (reviewed in Sfanos et al, 2012). Despite this, the possibility of a viral cause to PCa proved to be an exciting prospect, prompting follow-up studies in PCa as well as other diseases.…”

Section: The Story Of Xmrvmentioning

confidence: 99%

Infection of Xenotransplanted Human Cell Lines by Murine Retroviruses: A Lesson Brought Back to Light by XMRV

Hempel¹,

Burns²,

Marzo³

et al. 2013

Front. Oncol.

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Infection of xenotransplanted human cells by xenotropic retroviruses is a known phenomenon in the scientific literature, with examples cited since the early 1970s. However, arguably, until recently, the importance of this phenomenon had not been largely recognized. The emergence and subsequent debunking of Xenotropic Murine leukemia virus-Related Virus (XMRV) as a cell culture contaminant as opposed to a potential pathogen in several human diseases, notably prostate cancer and Chronic Fatigue Syndrome, highlighted a potential problem of murine endogenous gammaretroviruses infecting commonly used human cell lines. Subsequent to the discovery of XMRV, many additional cell lines that underwent xenotransplantation in mice have been shown to harbor murine gammaretroviruses. Such retroviral infection poses the threat of not only confounding experiments performed in these cell lines via virus-induced changes in cellular behavior but also the potential infection of other cell lines cultured in the same laboratory. Thus, the possibility of xenotropic retroviral infection of cell lines may warrant additional precautions, such as periodic testing for retroviral sequences in cell lines cultured in the laboratory.

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“…These emerging concerns led to intensive discussions and investigations of XMRV, including molecular and biological characterization of the virus and the development of assays, standards, and nonhuman primate (NHP) models for further studies of human infection and disease association. The results of several studies evaluating XMRV infection in humans indicated that the results of the original reports were due to sample and/or laboratory contaminations (12)(13)(14)(15)(16)(17)(18)(19). Furthermore, XMRV was found at high titers in the 22Rv1 human prostate cancer cell line (20) and was recently shown to have most likely originated from recombination between two different endogenous murine retrovirus sequences during derivation of the 22Rv1 human prostate cancer cell line by serial passage of a human prostate tumor xenograft in nude mice (21,22).…”

mentioning

confidence: 99%

No Evidence of Xenotropic Murine Leukemia Virus-Related Virus Transmission by Blood Transfusion from Infected Rhesus Macaques

Williams

Galvin²,

Gao

et al. 2013

J Virol

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The discovery of xenotropic murine leukemia virus-related virus (XMRV) in human tissue samples has been shown to be due to virus contamination with a recombinant murine retrovirus. However, due to the unknown pathogenicity of this novel retrovirus and its broad host range, including human cell lines, it is important to understand the modes of virus transmission and develop mitigation and management strategies to reduce the risk of human exposure and infection. XMRV transmission was evaluated by whole-blood transfusion in rhesus macaques. Monkeys were infected with XMRV to serve as donor monkeys for blood transfers at weeks 1, 2, and 3 into naïve animals. The donor and recipient monkeys were evaluated for XMRV infection by nested PCR assays with nucleotide sequence confirmation, Western blot assays for development of virus-specific antibodies, and coculture of monkey peripheral blood mononuclear cells (PBMCs) with a sensitive target cell line for virus isolation. XMRV infection was demonstrated in the virus-injected donor monkeys, but there was no evidence of virus transmission by whole-blood transfusion to naïve monkeys based upon PCR analysis of PBMCs using XMRV-specific gag and env primers, Western blot analysis of monkey plasma up to 31 to 32 weeks after transfusion, and coculture studies using monkey PBMCs from various times after transfusion. The study demonstrates the lack of XMRV transmission by whole-blood transfusion during the acute phase of infection. Furthermore, analysis of PBMC viral DNA showed extensive APOBEC-mediated G-to-A hypermutation in a donor animal at week 9, corroborating previous results using macaques and supporting the possible restriction of XMRV replication in humans by a similar mechanism.

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XMRV and prostate cancer—a 'final' perspective

Cited by 19 publications

References 66 publications

No Detection of Xenotropic Murine Leukemia Virus-Related Viruses in Prostate Cancer in Sanandaj, West of Iran

No Detection of Xenotropic Murine Leukemia Virus-Related Viruses in Prostate Cancer in Sanandaj, West of Iran

Infection of Xenotransplanted Human Cell Lines by Murine Retroviruses: A Lesson Brought Back to Light by XMRV

No Evidence of Xenotropic Murine Leukemia Virus-Related Virus Transmission by Blood Transfusion from Infected Rhesus Macaques

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