In-Depth Investigation of Archival and Prospectively Collected Samples Reveals No Evidence for XMRV Infection in Prostate Cancer

Abstract

XMRV, or xenotropic murine leukemia virus (MLV)-related virus, is a novel gammaretrovirus originally identified in studies that analyzed tissue from prostate cancer patients in 2006 and blood from patients with chronic fatigue syndrome (CFS) in 2009. However, a large number of subsequent studies failed to confirm a link between XMRV infection and CFS or prostate cancer. On the contrary, recent evidence indicates that XMRV is a contaminant originating from the recombination of two mouse endogenous retroviruses during passaging of a prostate tumor xenograft (CWR22) in mice, generating laboratory-derived cell lines that are XMRV-infected. To confirm or refute an association between XMRV and prostate cancer, we analyzed prostate cancer tissues and plasma from a prospectively collected cohort of 39 patients as well as archival RNA and prostate tissue from the original 2006 study. Despite comprehensive microarray, PCR, FISH, and serological testing, XMRV was not detected in any of the newly collected samples or in archival tissue, although archival RNA remained XMRV-positive. Notably, archival VP62 prostate tissue, from which the prototype XMRV strain was derived, tested negative for XMRV on re-analysis. Analysis of viral genomic and human mitochondrial sequences revealed that all previously characterized XMRV strains are identical and that the archival RNA had been contaminated by an XMRV-infected laboratory cell line. These findings reveal no association between XMRV and prostate cancer, and underscore the conclusion that XMRV is not a naturally acquired human infection.

Ductal variant of prostate adenocarcinoma harbor Xenotropic murine leukemia virus related virus (XMRV) infection: a novel finding in subtype of prostate cancer

“…[6] Lee et al [11] concluded that XMRV is not a naturally acquired human infection but rather a contaminant by an XMRV-infected laboratory cell line. Schlaberg et al [17] also shared the findings reported by Lee et al [11] In contrast, our present and previous in vitro analysis did not include any cell line; instead tumor samples from patients were used for analysis. Additionally, all necessary measures to avoid contamination, discussed in our previous published case-control study, has been taken into account.…”

“…[10] On the contrary, recent studies have reported the same virus, as a mere contamination of a PCa cell line. [6,11,12] Although, XMRV infection has been reported in prostate biopsies bearing adenocarcinoma, low prevalence of viral DNA was documented in our previous case control study, which included archival prostate biopsies diagnosed with cancer. [13] To date, extensive burden of PCa research is focused on broad spectrum of morphological differentiation; however investigation in etiopathogenesis of different histological subtype is largely neglected.…”

Xenotropic Murine Leukemia Virus-Related Virus (XMRV) and the Safety of the Blood Supply

“…The original group that found XMRV in prostate cancer samples published a paper showing that further analysis of prostate cancer samples showed no evidence of XMRV sequences (52). The major publications on the topic began to be retracted; one of the longest holdouts ended in 2014 when Schlaberg et al retracted their article describing the presence of XMRV in prostate cancer cells (53).…”

Concerns over the origin of NIH-CQV, a novel virus discovered in Chinese patients with seronegative hepatitis

“…The identification of a novel virus with the potential for bloodborne transmission such as NIH-CQV also has significant clinical and public health implications. Thus, it is critical that investigative studies on the validity of newly discovered pathogens be performed and reported in a timely fashion (1,3).…”