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The role of retroviruses in human life and disease

Human endogenous retroviruses (HERVs) have been the subject of a great deal of investigation in recent years. It has been established that HERVs cause some genetic diseases and there is strong circumstantial evidence for a link to some types of cancer and autoimmune diseases, but what else do we need to know about these unique organisms? In the December issue of the Journal of the Royal Society of Medicine, Dr Frank Ryan discusses HERVs in the context of medicine, human evolution and physiology.

Half of human DNA is viral
Although retroviruses were discovered in animals much earlier, their infectious potential for humans was not realized until the emergence of the leukaemia viruses, HTLV-I and II and, most dramatically of all, with the AIDS pandemic caused by viruses HIV1 and HIV2. As Dr Ryan explains, endogenous retroviruses (ERVs) 'have the unique ability to invade the germ cells of every species of vertebrate' where they are transmitted as part of normal reproduction (germline transmission), meanwhile interacting with their host's evolution over millions of years. 'Genome sequencing reveals that 8% of the human genome consists of HERVs and roughly half of our DNA is made up of viral genes or their genetic products.' So what are they really doing there?

Both useful and harmful to human life
The HIV-1 retrovirus pandemic is taking the lives of millions of people across the globe. However, HERVs also play a very important role in the normal human development and day to day existence. Three separate retroviruses supply vital components to every human pregnancy. If, as the public might imagine, we should remove these viruses from our chromosomes, the human species would become extinct. How do we reconcile these strange contradictions implicit in the behaviour of the viruses?

HERVs and symbiosis
Symbiosis is the partnership of two different life forms. It does not imply a friendly interaction. 'Certain microbes have entered into key symbiotic roles with their hosts to enable a kind of fast-track evolution,' Dr Ryan says. ‘We breathe oxygen thanks to ancient bacteria that once invaded our distant ancestor - the symbiotic descendants of these bacteria are the mitochondria in every living cell today.’ HERVs behave in much the same way. They begin as ‘aggressive symbionts’ – a complex form of parastism. But over time the relationship evolves to a ‘mutualistic symbiosis.’ In symbioses, natural selection operates not at the level of the selfish individual but at the level of the partnership, honing each partner in such a way as to strengthen the viability of the partnership, thus enabling it to become ‘an evolutionarily stable strategy.’ There is growing evidence that this symbiotic interaction with very large numbers of human retroviruses has played a major role in primate and most particularly human evolution.

Understanding the broader perspective
Dr Ryan emphasises the importance of understanding the symbiotic nature of HERVs to better understand their role in human diseases. 'It is not enough to demonstrate a virus, or a viral product, in tissues affected by cancer or disease. The viruses, or their products, may be playing a neutral or even a beneficial role. We first need to understand such symbiotic roles before we can recognise a pathological deviation that might contribute to a disease. This is likely to become of increasingly important to our understanding of certain cancers and autoimmune diseases.'

Full article [PDF 79k]
Editorial [PDF 31k]

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