New cancer virus: Merkel Cell Polyomavirus

About this time last year, I wrote a post on a new cancer virus, XMRV. I had some reservations about that paper I reviewed. I have some reservations about XMRV-->prostate cancer as a whole (Im just not convinced yet. at all.).

Its one thing to be skeptical about data, but its another to say 'Hey, thats a cool paper. They did something right!'

This paper isnt perfect. I have a lot of issues with it too-- BUT! I think it is a fantastic step in the right direction of establishing the role of a virus in a cancer and establishing the biochemistry of that interaction. This not only helps with the logic (there are some logical issues I have with XMRV-->prostate cancer) so people believe you, but if you elucidate the biochemistry/genetics/physiology, taking the issue beyond "WE CAN FIND THE VIRUS IN 80% CANKERS!", you can figure out potential avenues of treatment.

Merkel cell polyomavirus-infected Merkel cell carcinoma cells require expression of viral T antigens

Previously, this group of scientists has made a very important observation yet to be attained in XMRV research-- they looked at Merkel Cell Carcinoma lesions in patients for Merkel cell polyoviral insertion sites. MCV is not a retrovirus, any more than HPV is a retrovirus, but these guys can still accidentally integrate into genomes and cause cancer. And when they actually hunted down the integration sites, they found that MCV was in the genomes of the cancer cells in the same location (same location within patients, different patients had different integration sites. random event-->cancer). This is pretty damning evidence that the MCV insertion was actually causing the lesions, but there is still more to ask.

Is the virus causing cancer by insertional mutagenesis alone? Like, is it plopping into a tumor suppressor gene, or plopping upstream of a cancer gene?

Or is it some kind of side effect of the virus itself that is causing the cancer? Contrary to Creationist views of viruses, they are not just wrenches 'gumming up the works', to use Michael Behes phrase. They have their own tightly regulated replication cycles. If a virus accidentally inserts into a genome, it cant control what it is doing anymore. So a process that was once a nice, controllable feature of a virus, turns into an uncontrollable run-away freight train.

The latter is apparently what is happening with MCV and MCC.

MCV codes for a protein called a T-antigen. Because MCV is a DNA virus, it wants the host cells DNA-DNA polymerase so it can replicate the viral genome. T-antigens encourage the host cells to replicate (interfere with p53) so there is lots of DNA-DNA polymerase around, thus a lot of viral genome replication, thus lots of babby viruses. Pretty handy trick!

Not so handy anymore when a virus accidentally integrates, and the T-antigen wont turn off. You just keep making more and more, it keeps interfering with p53, the cells cant stop dividing. The cells cant go through apoptosis. What does that mean? Cancer.

What is neat about this paper is not that '80% of Merkel Cell Carcinoma is caused by MCV!'. Its not 'All the tumors have integrated MCV!'. Its not 'All people with MCC have antibodies to MCV!'

Whats neat is that they demonstrate that the integrated MCV T-antigen is what is causing the trouble. When you get rid of the T-antigen via siRNA (the message is still made, you cant get rid of the DNA, but siRNA can get rid of the mRNA so the protein cant be made anymore) you get rid of the cancer phenotype. 'Oncogene addiction'. The cells go back to normal. Its not just an observation-- its an answer behind the why? for the observation.

Is this paper perfect? No. But its a hellovalot better than the trend I have noticed with Nature/Science/the major PLOSs-- Give front page to 'OMFG LOOK AT THIS OBSERVATION!!!! ITS TOTALLY NOVEL AND OVERTHROWS EVERYTHING WE KNOW!!!! THIS EXPLAINS EVERYTHING!!!' when observations can be wrong. Interpretations of observations can be wrong.

The real meat-and-potatoes of science is understanding the "Why?" behind observations. But it appears fundamental science has become unfashionable in 'high impact journals'. Cool, sexy, maybe wrong observation was in Science, the real science was in Journal of Virology. Lame.