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Thursday 29 July 2010
Abstract from 12th International Conference On Malignancies In AIDS And Other Acquired Immunodeficiencies (ICMAOI) April 26-27, 2010, NIH Main Campus (US).
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 to XMRV and infected patients are viremic.
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.
References
1. Schlaberg et al.: XMRV is present in malignant prostate epthelium 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
Ruschetti, F et al (2010) 'Repeated Detection of Infectious Xenotropic Murine Virus-Related Virus (XMRV) in Human Neoplasia and Neuroimmune Diseases (listed as 'Pathogenic Consequences of Xenotropic Murine Virus-related Virus (XMRV) Expression in the Development of Chronic Diseases', from the Program Book: 12th International Conference On Malignancies In AIDS And Other Acquired Immunodeficiencies (ICMAOI) April 26-27, 2010, NIH Main Campus, National Cancer Institute, p. 33.
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.
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.