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.