Viruses and the human genome: new perspectives on an old relation
Viral infection susceptibility varies amongst individuals, with some people exposed to viruses for long periods of time but remaining uninfected nonetheless. The burning question is why? Italian researchers at the Scientific Institute for research, hospitalization and health care E. Medea (IRCCS), the University of Milan and the Politecnico di Milano have unlocked the mystery, and their work could lead to novel treatments to fight infection. The results of their study, funded in part by the EU, were published in the Public Library of Science (PLoS) Genetics journal. It's no secret that genetics play a crucial role in viral infection susceptibility. But the specific protective variants identified to date are thought to capture only a small portion of the total genetic variation. It's likely that other genetic variants are still out there. Keen to get to the bottom of this, the researchers analysed the genomes of 52 populations from different parts of the world with exposure to a wide range of viruses. Their findings are part of the EU-funded EMPRO ('European microbicides project'), AVIP ('AIDS vaccine integrated project') and NGIN ('Next generation HIV-1 immunogens inducing broadly reactive neutralising antibodies') projects. EMPRO and AVIP received EUR 11.8 million and EUR 10.3 million respectively under the 'Life sciences, genomics and biotechnology for health' Thematic area of the EU's Sixth Framework Programme (FP6). The NGIN project is supported under the Health Theme of the Seventh Framework Programme (FP7) to the tune of EUR 7.53 million. Viruses have for centuries ranked with wars and famine on the list of major challenges to human progress and survival. On top of that, studies have shown that once they infect the chemical code from which all genetic material is made, viruses reside within us, carrying a record that goes far back in time. When the mapping of the human genome was completed in 2003, scientists were confronted with a startling fact: our body is littered with the shards of so-called endogenous retroviruses. But what role has this viral DNA (deoxyribonucleic acid) played in our evolution, and what is it doing to our physiology? To answer these questions, the Italian researchers searched the human genome for evidence of natural selection - the evolution of favourable genetic mutations - during the past 200 000 years of human evolution. Their study looked specifically at mutations in chromosomes called 'single nucleotide polymorphisms,' or SNPs (pronounced 'snips'). Over time, chromosomes randomly break and recombine to create new variants of the chromosome. If a favourable mutation appears, then the number of copies of that chromosome will increase rapidly in the population because people with the mutation are more likely to survive and reproduce. The researchers questioned whether the high incidence of viruses at places where the climate provided friendly conditions, such as warm, wet regions of Africa, translated into increased numbers of these genetic mutations. By linking the number of different mutations with viruses, the researchers found that more than 400 different mutations in 139 genes heavily affect people's risk of catching viruses. As expected, many of these genes had been selected and more genetic mutations spread through populations that are infected by many different viruses. Based on these findings, they extrapolated that many of these genes make us more or less susceptible to viruses. While the results of this study are far from conclusive, the researchers have succeeded in shedding light on an issue that has wracked the brains of many over the years. Next on the to-do list for the following couple of years is to conduct follow-up studies in larger human groups that should provide more definitive answers. Until then, IRCCS' Dr Manuela Sironi and her colleagues propose that this combined approach could also be used to find genes that boost or cut the risk of infections from other bugs such as bacteria.
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