Friday, November 19, 2010

Stowaway Viruses

Most of us tend not to think too much about viruses until we (or our computers...) get one, and then we start to wonder what medical science is up to if after all this time we still don't have a cure for viral disease.

What we don't realize is that lurking in our genomes, and indeed the genomes of most animals, are viral stowaways. Biologists are no strangers to stowaways - the mitochondrion is one of the best examples, once a free-living bacterium now captured to be the energy generators of the eukaryotic cell. But at least one can see a mitochondrion. Stowaway viruses, more properly called endogenous viral elements (EVEs), have worked their way right into the stuff of life itself, inserting the instructions for making more of themselves into our DNA.

For one group of viruses, the retroviruses, this does not come as a surprise. Retroviruses invade the cell carrying their genomes on RNA, and then use the enzyme reverse transcriptase (hence their name) to write their genome into DNA which is then inserted into the host genome. From this seat in the host genome, their genes are activated and set in motion the machinery for producing and assembling new virus particles. They can also lie quiescent for generations, piggybacking along the divisions of their (increasingly numerous) hosts. It's been known for a long time that much of the human genome is made up of former EVEs that have mutated and are no longer functional, becoming part of the 'junk DNA' that litters our genomes.

A recent intensive search of animal genome sequences, however, has found that non-retroviruses can form EVEs too. This is part of a clutch of recent studies on the diversity and evolution of EVEs, that seems to also pose a philosophical question - what does it really mean to be human? The human cells in our bodies are already outnumbered by the bacteria that live in our gut, on our skin, under our nails, and virtually every other surface on us. And now we find that our genomes don't really belong to us either?

EVEs in the genome sequence are being used as a 'fossil record' of viral infection events in our human past, being of value in reconstructing the history of virus and human evolution. Yet these ancient events still have very immediate consequences for us today. Schizophrenia is a widespread and serious mental disorder that is extremely debilitating to its sufferers. It has long been treated as a purely psychiatric disorder, with the exact physiological basis remaining obscure. Yet some puzzling observations about the disease remained:

Schizophrenia is usually diagnosed between the ages of 15 and 25, but the person who becomes schizophrenic is sometimes recalled to have been different as a child or a toddler—more forgetful or shy or clumsy. Studies of family videos confirm this. Even more puzzling is the so-called birth-month effect: People born in winter or early spring are more likely than others to become schizophrenic later in life. It is a small increase, just 5 to 8 percent, but it is remarkably consistent, showing up in 250 studies. That same pattern is seen in people with bipolar disorder or multiple sclerosis.

This observation has been used to support the hypothesis that schizophrenia is caused by an EVE called HERV-W, which has also been implicated in the onset of multiple sclerosis. Although the endovirus theory of schizophrenia is still far from being textbook truth (the theory's main supporter, Fuller Torrey, has weathered considerable controversy), it is certainly thought-provoking, and will certainly draw more attention to the burgeoning field of animal endoviruses.

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