Moselio Schaechter


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« Where Mathematicians & Biologists Meet | Main | Cell Division Through DNA Curtains »

May 24, 2012

Fine Reading: Endogenous Retroviruses

by Elio

I can't think of anything more startling, more promising, and more intractable in biology than the business of endogenous retroviruses. They seem to be ubiquitous in both invertebrates and vertebrates, and even in plants. In humans, they make up at least 8% of the genome, plus some bits and pieces. They are ancient; in our lineage they go back perhaps 100 million years. Let's face it, if we hadn't been told about them, we could never have conjured up such a strange story. It’s like hearing that you possess a limb or an organ that you didn't know about.

The very existence of endogenous retroviruses (ERVs) touches us in a number of ways. How is evolution shaped by the acquisition of such viral packets of genes? How often has it happened? Did it arise by infection, as seems likely? Is this an ongoing process that leads to further evolution? What does this have to do with the evolution of viruses? What does it reveal about the regulation of gene expression? On balance, do they do more good or more harm? All these questions have arisen elsewhere, but they are brought to the fore by these strange entities.

There is much to be learned, but certain facts stand out. A striking example of the good ERVs have done is seen in the case of the syncytin gene, whose product is involved in some essential way in the development of the placenta. It is thought that ERVs may also play a role in the immunosuppression needed to avoid fetal rejection by the mother. On the other hand, can they cause cancer? With some laboratory-induced exceptions, ERVs have not been found in tumors. On the other hand, ERVs in humans and great apes control the formation of a protein (GTAp63) that protects the germ line from cancers. In addition, ERVs may contribute to resistance to exogenous retroviruses. So much for viruses being “bad.”

It follows that knowing about endogenous retroviruses should be part of the education of all biologists, not just retrovirologists. I recommend a review by Jonathan Stoye entitled Studies of Endogenous Retroviruses Reveal a Continuing Evolutionary Saga. Here you will find a clearly written account of ERV genomic architecture, reproductive cycle, and phylogeny. Also discussed are some of the consequences of their presence, including the expression of viral proteins, the control of host processes by ERVs, and their cost-benefit balance. The complex subject of controlling retroviral replication is explained with clarity, as is the evolutionary interplay between the ERVs and their host. You might as well start somewhere, and this is a good place for it.

Comments

MRV retroviruses are the more likely cause of several neurodegenerative diseases.

As we know those viruses have not been detected when researchers have failed to clinically validated their assays and have only optimised to a synthetic made made strain. All studies that have performed this simple step have found the viruses associated with certain diseases

I was mindblown when I discovered endogenous retroviruses when doing an assignment on prions and transmissible spongiform encephalopathies. To an extent, I now hold a belief that neurodegenerative disease associated proteins e.g prions, amyloid-beta, alpha-synuclein, DNA TAR Binding protein 43 and so on are actually endogenous retroviruses that have integrated into our genome as part of our brain's innate immune system to protect it against viruses etc. If you look at this way, it could possibly be said that these neurodegenerative diseases are actually 'auto-immune'. That's throwing it out there. My belief was developed through this great and stimulating read on the evolution of the prion protein http://precedings.nature.com/documents/3887/version/1 . However I know as a science student we need to look at it from different perspectives and evidence on both sides.

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