Detection of an Infectious Retrovirus, XMRV, in Blood Cells of Patients with Chronic Fatigue Syndrome

Lombardi, Vincent; Ruscetti, Francis W.; Gupta, Jaydip Das; Pfost, Max A.; Hagen, Kathryn S.; Peterson, Daniel L.; Ruscetti, Sandra K.; Bagni, Rachel; Petrow‐Sadowski, Cari; Gold, Bert; Dean, Michael; Silverman, Robert H.; Mikovits, Judy A.

doi:10.1126/science.1179052

Cited by 489 publications

(793 citation statements)

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“…If it can be proven that XMRV infection is indeed widespread and can cause prostate cancer and/or other human diseases (1,21,34,41), it is important to identify effective antivirals against this virus. Toward this end, recent studies have shown that HIV-1 RT inhibitors, such as azidothymidine (AZT) (33,35), zidovudine (ZDV), and tenofovir disoproxil fumarate (TDF), as well as the integrase inhibitor raltegravir (35), can inhibit XMRV replication in cell culture to various extents, suggesting that they can be used either individually or as a combination therapy to treat XMRV infection (33,35).…”

Section: Discussionmentioning

confidence: 99%

Evaluation of Cellular Determinants Required for In Vitro Xenotropic Murine Leukemia Virus-Related Virus Entry into Human Prostate Cancer and Noncancerous Cells

Bhosle¹,

Suppiah²,

Molinaro³

et al. 2010

J Virol

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Prostate cancer is the most common male malignancy in Western countries and the second most common cause of cancer-related deaths in males worldwide (15,24). The known risk factors for prostate cancer are hormones (i.e., androgens), diet, sex, and race, as well as environmental and genetic factors (27). A recent study suggests that susceptibility to prostate cancer can be influenced by the genetic variations associated with an antagonistic coevolution, which occurs between a specific host locus (RNASEL), known to be involved in antiviral innate immune defense, and a viral pathogen (38). Indeed, several epidemiologic studies have supported the involvement of the RNASEL gene in the prostate cancer etiology (4,5,30,31), whereas other studies do not (9,22,34,43). Some studies have reported that individuals with a single mutated copy of the RNASEL gene have a 50% increased risk for prostate cancer, whereas those with homozygous mutant RNASEL alleles have a 2-fold-increased risk of prostate cancer (5).The RNASEL gene encodes for the RNase L protein, a constitutively expressed latent endoribonuclease, which mediates the interferon-inducible 2-5A system against viral and/or cellular double-stranded RNAs (8,16,20,23,49,50). The RNase L "Q" variant allele (R462Q) shows a 3-fold decrease in catalytic activity compared to the wild-type enzyme (5, 44). The possible association of mutant RNASEL alleles with human prostate cancers suggests an enhanced susceptibility of prostate tissues to a viral agent. This hypothesis has led to the recent identification of a new human retrovirus, xenotropic murine leukemia virus (MuLV)-related virus (XMRV), in 40% of prostate cancer patients with the QQ variant alleles of RNASEL compared to 1.5% among heterozygous (RQ) and wild-type (RR) RNASEL carriers (41). XMRV virus infection appears to be susceptible to inhibition by interferon and its downstream effector RNase L protein (7). However, a recent study has provided some evidence to show that XMRV infection is independent of the RNASEL genotype (34), suggesting that population differences and/or other environmental or genetic factors may influence the impact of RNASEL on prostate cancer development.The XMRV genome is 8,185 nucleotides in length and shares up to 95% overall nucleotide sequence identity with known xenotropic MuLVs (41). One receptor for xenotropic MuLVs is Xpr1, a 696-amino-acid protein with multiple transmembrane-spanning domains (2). Expression of this protein in Chinese hamster ovary (CHO) cells that are not known to express Xpr1 endogenously confers an enhanced susceptibility of these cells to xenotropic MuLV infection (2). Infection of hamster and mouse cells with XMRV-like virus that is derived from a prostate cancer cell line (22Rv1) also requires Xpr1 as a receptor (18). Earlier studies have demonstrated the importance of certain residues located within the putative third and fourth extracellular loops (ECL3 and ECL4) of Mus dunni's Xpr1 in conferring infection by xenotropic MuLVs (25). Furthermore, it has been shown ...

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Section: Discussionmentioning

confidence: 99%

Evaluation of Cellular Determinants Required for In Vitro Xenotropic Murine Leukemia Virus-Related Virus Entry into Human Prostate Cancer and Noncancerous Cells

Bhosle¹,

Suppiah²,

Molinaro³

et al. 2010

J Virol

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“…Thus, the role of XMRV in human pathogenesis is controversial (Switzer et al, 2011). XMRV was also reported to be presence in patients with chronic fatigue syndrome (CFS) (Lombardi et al, 2009). However, the link between XMRV and CFS is unclear, because in other studies it has failed to detect XMRV infection in CFS patients Groom et al, 2010;Switzer et al, 2010;van Kuppeveld et al, 2010;Knox et al, 2011;Satterfield et al, 2011;Shin et al, 2011).…”

Section: Introductionmentioning

confidence: 99%

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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“…In der Mehrzahl der später veröffentlich-ten Studien wurde XMRV jedoch in keiner einzigen Probe nachgewiesen [8,9,10,11,12,13]. Bei Wiederholungsuntersuchungen von zuvor am WPI im Rahmen der initialen Studie [3] positiv getesteten CFS-Patienten konnten in unabhängigen Laboren in keinem einzigen Fall XMRV oder spezifische Antikörper gegen XMRV-Proteine nachgewiesen werden, obwohl nahezu identische, hochsensitive Verfahren verwendet wurden [14,15]. Hiermit stellt sich die Frage, was die Ursache für den beschriebenen Nachweis von XMRV am WPI und an einem kommerziellen Labor sowie in den anderen Studien sein könnte.…”

Section: Ursprüngliche Einschätzung Von Xmrv Als Neues Retrovirus Mitunclassified

“…Heute gilt als gesichert, dass alle XMRV-Sequenzen aus der 22Rv1-Zelllinie stammen. Unter Berücksichtigung der oben angeführ-ten Argumente stellt sich daher die Frage nach der Validität der Untersuchungsergebnisse, die in den Arbeiten über positive XMRV-Diagnosen in Patientenproben beschrieben wurden [3]. …”

Section: Entstehung Von Xmrv In Einer In Mäusen Etablierten Humanen Punclassified

XMRV ist nicht human-pathogen und hat keine Bedeutung für die Sicherheit von Blut und Blutprodukten

2012

Bundesgesundheitsbl.

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Der Arbeitskreis Blut des Bundesministeriums für Gesundheit gibt als nationales Beratungsgremium Stellungnahmen zu neuartigen Erregern ab, bewertet neue Erkenntnisse zu bekannten Erregern und erarbeitet entsprechende Empfehlungen für die Fachöffentlich-keit. Diese Serie von Stellungnahmen zu einzelnen Erregern werden als Zusammenfassung des aktuellen Wissensstandes veröffentlicht, speziell unter transfusionsmedizinisch relevanten Aspekten (Bundesgesundhbl., 41, 53, 1998).Frühere Beiträge befassten sich mit der Creutzfeldt-Jakob-Erkrankung, dem

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Detection of an Infectious Retrovirus, XMRV, in Blood Cells of Patients with Chronic Fatigue Syndrome

Cited by 489 publications

References 26 publications

Evaluation of Cellular Determinants Required for In Vitro Xenotropic Murine Leukemia Virus-Related Virus Entry into Human Prostate Cancer and Noncancerous Cells

Evaluation of Cellular Determinants Required for In Vitro Xenotropic Murine Leukemia Virus-Related Virus Entry into Human Prostate Cancer and Noncancerous Cells

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

XMRV ist nicht human-pathogen und hat keine Bedeutung für die Sicherheit von Blut und Blutprodukten

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