Repeated Detection of Infectious Xenotropic Murine Virus-Related Virus (XMRV) in Human Neoplasia and Neuroimmune Diseases – Source: 12th Intl. Conf. on Malignancies in AIDS and Other Acquired Immunodeficiences, Apr 26, 2010

(Note: This abstract, of a presentation given April 26 by National Cancer Institute researcher Frank Ruscetti, is listed in the conference agenda & program book  as “Pathogenic Consequences of Xenotropic Murine Virus-Related Virus (XMRV) Expression in the Development of Chronic Diseases.” “Neoplasia” refers to abnormal tissue proliferation, as in a tumor.)

Background: In 2006, sequences of a novel human retrovirus, XMRV, were identified and reported to be associated with a subset of hereditary prostate cancer. Although the public health implications of this finding were not immediately clear, two recent papers show XMRV is clearly a health concern.

• One clearly shows that XMRV expression in the proliferating prostate stroma and epithelium of prostate cancer patients [1].

• The second describes the detection of XMRV in about two-thirds of patients diagnosed with chronic fatigue syndrome [2].

We will present data that in these and other neuroimmune diseases and cancers, the host mounts a humoral response [involving antibodies] to XMRV and infected patients are viremic [virus particles in the bloodstream].

Methods: A combination of classical retroviral methods, including RT-PCR, full-length genomic sequencing, immunoblotting of viral expression in activated PBMC, passage of infectious virus in plasma and PBMC to indicator cell lines, and presence of antibodies to XMRV in plasma, allowed XMRV detection in more than 75% of the CFS patients studied.

Since then, several publications in Europe using DNA-PCR of blood products failed to detect XMRV sequences in patients with either disease and have created considerable controversy. Reliable methods for the biological and molecular amplification to detect XMRV in unstimulated blood cells and plasma have been developed.

Some DNA-PCR negative patient blood samples represent false negatives, and molecular analysis using DNA from unstimulated blood cells is not yet sufficient for XMRV identification.

Results: In mice, viruses related to XMRV cause B-cell lymphoma usually by insertional mutagenesis activating a cellular oncogene as well as causing chronic neurological diseases.

We will present a case of development of such B cell lymphoma in CFS patients.
XMRV-infected individuals with both neuroimmune disease and cancer develop an immune response to XMRV.

The isolation of infectious XMRV from prostate cancer patients will be shown for the first time. Pathogenic consequences of this infection will be discussed

Conclusion: XMRV, a retrovirus of unknown pathogenic potential, is infectious in humans.

1. Schlaberg et al.: “XMRV is present in malignant prostate epithelium and is associated with prostate cancer.” Proc Natl Acad Sci U S A 106:16351, 2009.
2. Lombardi et al.: “Detection of an infectious retrovirus, XMRV, in blood cells of patients with chronic fatigue syndrome.” Science 326:585, 2009.

Source: Ruscetti F, Lombardi V, Pfost M, Hagen K, Mikovits J. Laboratory of Experimental Immunology, NCI-Frederick, Frederick, Maryland; Whittemore-Peterson Institute, University of Nevada, Reno, Nevada, USA

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