A large part of our DNA is made up of genes from ancient viruses that have accumulated in our genome during evolution but can no longer replicate. Researchers have now shown that in mice with compromised immune systems, exposure to bacteria (including those that naturally live in our bodies) may enable these ancient viruses to reactivate, causing infections and eventually cancer.
"This work suggests that the part of our genome which originates from these ancient viruses - called endogenous retroviruses (ERVs) - harbours elements that may pose a threat to human health," said George Kassiotis of the MRC's National Institute for Medical Research (NIMR; now part of the Francis Crick Institute).
Dr Kassiotis and Jonathan Stoye's teams at NIMR worked with colleagues at the National Cancer Institute in Frederick, USA, and the Centre d'Immunologie de Marseille-Luminy in France. They studied mice bred with immunodeficiencies that affected their production of antibodies and monitored pathogenic viruses that emerged from ERVs in the mouse DNA. Antibodies allow healthy immune systems to identify and fight infections, meaning that this capability was missing in the study mice.
The mice spontaneously developed infections with a virus called ecotropic murine leukaemia virus (eMLV), which then triggered the development of lymphoma. eMLV is one of the viruses that has become incorporated into the mouse genome over time but under normal circumstances is unable to replicate itself. Interestingly, pathogenic retroviruses were not found in mice that were bred without bacteria in their gut, showing that these microbes played a role in reactivating the ERVs.
Dr Kassiotis explained: "ERVs are generally unable to replicate in our cells, partly due to mutations that have made them inactive. Their potential effects on health or disease were not known.
"Our results show that, when immune systems are compromised, increased exposure to other microorganisms - such as gut bacteria - drives ERVs to repair their replication defects and give rise to fully infectious viruses that cause cancer."
The paper, ' Resurrection of endogenous retroviruses in antibody-deficient mice', is published in Nature.
