First "formal" salvo?
Abstract from 12th International Conference On Malignancies In AIDS
And Other Acquired Immunodeficiencies (ICMAOI)
April 26-27, 2010
Lister Hill Auditorium
NIH Main Campus
http://oham.cancer.gov/objects/pdf/2010ICMAOI_Program_Book.pdf (p. 33)
http://www.capconcorp.com/meeting/12thICMAOI/agenda.asp
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P7. 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' on website)
Francis Ruscetti1, Vincent Lombardi2, Max Pfost2, Kathryn Hagen2, Judy
Mikovits2
1Laboratory of Experimental Immunology, NCI-Frederick, Frederick, MD, USA
2Whittemore-Peterson Institute, University of Nevada, Reno, NV, USA
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.
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