Inverted viruses
Viral DNA in the human genome helps fight pathogens
Ivan Zagorsky, Vesti
Almost eight percent of human DNA consists of fragments of viral origin, which remained from the struggle of our ancestors with diseases. For a long time it was believed that these random sections of the genetic code do not perform any function. But a new study shows that our body has turned some of them into weapons against modern viruses. Scientists from the University of Utah believe that parts of viral DNA embedded in the human genome can affect the genes responsible for innate immunity, which is the first line of defense against pathogenic organisms.
After penetration into human germ cells, retroviruses synthesize a DNA fragment based on their RNA and embed it into the genome of an infected organism to create their own copies. After millions of years of evolution in the descendants of creatures who survived the disease (and survived after it), such areas lose the ability to express genes and accumulate in cells in the form of inactive hereditary elements.
Cedric Feschotte and his colleagues found that the removal of these fragments, known as "endogenous retroviruses", leads to a violation of the immune system.
The effectiveness of the immune system largely depends on the rapid coordinated response of all components involved in this process. When infected, cells send a chemical alarm signal, releasing interferon proteins, and with their help force neighbors to activate hundreds of genes aimed at fighting pathogens.
A team of biologists analyzed publicly available information about elements of the human genome and found thousands of endogenous retroviruses that are stored in human DNA and can be activated by interferons. Scientists also drew attention to the fact that the viral sites are not randomly scattered throughout the genome, but are collected near the genes that ensure the functioning of the immune system.
To establish the role of endogenous retroviruses, the researchers used the state-of-the-art CRISPR/cas9 genome editing tool and alternately deleted viral sequences in cell cultures. It turned out that without some fragments, immune genes could not be properly activated in response to the interferon signal. In addition, when cells were deprived of sites located next to the AIM2 immunity gene, their ability to resist the attack of viruses was greatly reduced.
These results show that ancient viral DNA has become an important part of the defense mechanism by which cells fight modern pathogens.
"The response to interferon can be compared to turning on a cellular alarm system, and we found that some of the most important switches in this system actually originate from ancient viruses," explains study co–author Edward Chuong in a press release from Ancient Viral Invaders in Our DNA Help Fight Today's Infections.
Researchers believe that fragments of foreign DNA could have been included in the immune system for a reason. In their opinion, pathogens are constantly evolving and changing the tactics of attack and, in order to keep up, organisms have learned to usefully use the captured genetic material against the viruses themselves.
More information about the results of the work of American scientists can be found in the article Chuong et al. Regulatory evolution of innate immunity through co-option of endogenous retroviruses, published in the journal Science.
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10.03.2015