Ancient viruses in modern humans

Researchers at Oxford and Plymouth Universities have discovered ancient viruses from Neanderthals in the DNA of modern humans. Their research was supported by the Wellcome Trust and Medical Research Council (MRC) and published in the journal Current Biology.

The researchers explained that high-throughput sequencing technology can reveal the genomes of extinct human groups such as Neanderthals and Denisovans and, in those genomes, sequences of viral origin (endogenous retroviruses, or ERVs). They say previous research conducted by the Albert Einstein College of Medicine could not locate the integration site of ERVs (locus) in humans, the conclusion of which was that the retroviruses infected “the germline of these archaic hominins at or subsequent to their divergence from modern humans (∼400,000 years ago)”.

However, when the UK researchers compared genetic data from fossils of Neanderthals and Denisovans to that of modern-day cancer patients, they found evidence of the ancient viruses in the modern human DNA. This suggests that the viruses originated in our ancestors, around 800,000 years ago, and will enable scientists to further investigate possible links between ancient viruses and modern diseases.

For each locus recovered in modern humans, the top sequence with black background shows the corresponding pre-integration region in the human reference sequence (hg19) and below are the reads from both the archaic hominins (with the viral regions in blue) and modern humans (viral regions in red). ‘De’ = Denisovan, ‘Ne’ = Neanderthal. In most cases there are reads spanning both upstream and downstream boundaries of the ERV, with the characteristic six base target site duplication (TSD) of the host genome between them. An asterisk shows the first base of the ERV, which in five of the seven instances represented has integrated in reverse orientation.

ERVs pass from generation to generation and make up around 8% of human DNA - part of the 90% with no known function (‘junk’ DNA). Dr Gkikas Magiorkinis, an MRC Fellow at Oxford University’s Department of Zoology, explained, “Under certain circumstances, two ‘junk’ viruses can combine to cause disease - we’ve seen this many times in animals already. ERVs have been shown to cause cancer when activated by bacteria in mice with weakened immune systems.”

Dr Magiorkinis and his colleagues are looking to further investigate whether the ancient viruses, belonging to the HML2 family of viruses, have links with cancer and HIV. He noted, “How HIV patients respond to HML2 is related to how fast a patient will progress to AIDS, so there is clearly a connection there.

“HIV patients are also at much higher risk of developing cancer, for reasons that are poorly understood,” Dr Magiorkinis continued. “It is possible that some of the risk factors are genetic and may be shared with HML2. They also become reactivated in cancer and HIV infection, so might prove useful as a therapy target in the future.”

The team is also investigating whether the viruses are still active or able affect a person’s risk of developing diseases such as cancer, using a combination of evolutionary theory, population genetics and genetic sequencing technology.

“Using modern DNA sequencing of 300 patients, we should be able to see how widespread these viruses are in the modern population,” said Dr Robert Belshaw of Plymouth University, who led the research. “We would expect viruses with no negative effects to have spread throughout most of the modern population, as there would be no evolutionary pressure against it. If we find that these viruses are less common than expected, this may indicate that the viruses have been inactivated by chance or that they increase mortality; for example, through increased cancer risk.

“Within the next five years, we should be able to say for sure whether these ancient viruses play a role in modern human diseases.”

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