Researchers in Switzerland have unravelled part of the mystery of dormant endogenous retroviruses (ERVs) found in our DNA which, if woken, 'multiply, induce innumerable mutations' and kill embryos at an early stage of development, as reported by the publication Scientific Computing.
Previous research has revealed the existence of these 'viral squatters', however, how the body silences them to prevent the adverse consequences of their presence has been little understood until the current study. 'These data indicate that KAP1 has a crucial role in controlling ERVs during early embryonic development,' write Didier Trono and his team from Ecole Polytechnique Federale de Lausanne, in the journal Nature.
The team analysed early mouse embryos and embryonic stem cells, and found a master regulatory protein called KAP1 which 'can trigger permanent gene silencing during embryogenesis,' the researchers explain. When they removed the gene, the damaging mutations caused by increasing activity in the ERV receptors increased by more than 500 times, which caused the cells and embryos to die.
In mutating their host's DNA, these ERVs have the power to alter genes. However, over time, the human body has evolved to silence their effects. Trono notes that 'in our genome, we find traces of the last two major waves [of evolution]. The first took place 100 million years ago at the time when mammals started to develop, and the second about 50 million years ago, just before the first anthropoid primates.'
It has been suggested that the approach could be used as a potential target against AIDS (acquired immune deficiency syndrome). Where the AIDS virus lies dormant in infected red blood cells, if these ERVs were 'woken', they may be more susceptible to therapy. 'The work presented here opens new perspectives to explore ERV-mediated control of cellular genes in development and in adult tissues,' Trono and his team conclude.