Thursday, May 5, 2011

Polyoma Virus Information


This stuff is beyond my ability to comprehend, but from what I can put together, the story is like this.
In the 1950's, there was pressure to begin inoculating the general population against Polio. This came both from the general population as there was a high level of anxiety about the disease which caused paralysis and death among many of its victims, and also from the companies racing to get the vaccines on the market for financial gain.
The initial doses of the vaccine were harvested from monkey kidneys and the virus was inactivated by formaldehyde. The Polyoma Virus was a contaminant, slightly more hardy and not inactivated by the amounts used. I have read some estimated of up to 50,000,000 doses of the vaccine were contaminated before they switched breeds of monkeys. The vaccine was given in the mid 50's.
The evidence of a cause and effect relationship between MCC and the virus is circumstantial. The virus is present in 80% of MCC patients in the USA, but not more than 60% of the general population. People with a reduced immune response are more susceptible to the disease.
MCC can be effectively treated locally by Beta Interferon, injected locally. Beta Interferon is an anti-viral drug.
The Polyoma virus is not found in MCC cases in Australia.
Please Note. The virus has mutated  and there is no threat of human to human transmission of the virus. 
Below are some abstracts.
Merkel cell polyomavirus and MCC
2008: Feng, Moore, Chang discovered a new human polyomavirus, the Merkel cell polyomavirus Virus integrates in the genome of most MCC tumors in a clonal pattern (Feng H et al., Science 2008) Viral DNA present in ~80% MCC tumors MCPyV proteins are present and persistently expressed in > 50% of the tumors
~60% of US population has specific antibodies to the MCPyV capsid protein (Carter JJ et al., J Natl Cancer Inst. 2009) ~90% of MCC patients are sero-positive to the MCPyV capsid protein supporting a continuing role for this new virus in most MCC tumors
Mutation pattern in the large T oncoprotein are highly suggestive of a role in this cancer (N terminal – pro-cell cycle portion is conserved: C terminal – genomic instability generating region is deleted in most tumors) (Shuda et al., Proc Natl Acad Sci U S A. 2008)
Additional References:
1. Garneski KM, Decaprio JA, Nghiem P. Does a new polyomavirus contribute to Merkel cell carcinoma? Genome Biol 2008; 9(6):228.  Click here for a PDF.
A review of polyomavirus biology and its possible relation to cancer.
2. Garneski KM, Warcola AH, Feng Q, Kiviat N, Leonard JH, Nghiem P. Merkel Cell Polyomavirus Is More Frequently Present in North American than Australian Merkel Cell Carcinoma Tumors. Journal of Investigative Dermatology 2009; 129, 246–248.  Click here for a PDF.
North American and Australian tumor samples were evaluated for presence of MCPyV and a higher incidence in North American samples were positive for MCPyV when compared to Australia, suggesting a possible strain variant.
3.  Feng H, Shuda M, Chang Y, Moore P.  Clonal Integration of a Polyomavirus in Human Merkel Cell Carcinoma.  Science 2008; 319:1096-1100
A technique called digital transcriptome subtraction (DTS) was used to identify a new virus, which is a previously unknown polyomavirus that we call Merkel cell polyomavirus (MCV or MCPyV).  MCPyV sequences were detected in 8 of 10 (80%) MCC tumors (lower incidence in non-MCC tumors).
4.  Carter J, Paulson K, Wipf G, Miranda D, Madeleine M, Johnson L, Lemos B, Lee S, Warcola A, Iyer J, Nghiem P, Galloway D.  Association of Merkel Cell Polyomavirus–Specific Antibodies With Merkel Cell Carcinoma Journal of the National Cancer Institute2009; [Epub ahead of print].  Click here for a PDF.
Merkel cell polyomavirus (MCPyV) has been detected in approximately 75% of patients with the rare skin cancer Merkel cell carcinoma. We investigated the prevalence of antibodies against MCPyV in the general population and the association between these antibodies and Merkel cell carcinoma.

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