28 September 2022

Former enemies have become allies

Retrovirus genes protect mammalian brains from new pathogens

Daniil Sukhinov, Naked Science

Many viruses — from the common influenza virus and SARS-CoV-2, which causes Covid-19 coronavirus infection, to HIV — undoubtedly have a great impact on a person's daily life, literally taking him out of his usual rhythm for several days or weeks, and sometimes for the rest of his life. However, a number of viruses that infected but did not kill our ancestors millions of years ago left a much more serious trace in the form of their DNA in the genome of both humans and other mammals.

Subsequently, these viral genes changed and evolved, acquiring over time completely new functions that are already useful for the host organism. Thus, endogenous retroviruses, whose DNA is embedded in the host organism and has ceased to show pathogenic effects, turn into retrotransposons — sections of the genome capable of repeatedly copying themselves and embedding back into the genome, but in a new place.

Sometimes such retrotransposons perform extremely important functions in the host body — from the formation, maintenance and endocrine regulation of the mammalian placenta, to participation in the development of fetal/newborn muscles and regulation of brain functions. In a new work, a team of scientists from Japan revealed the function of another pair of retrotransposons — RTL5 and RTL6. The authors described the results of the study in an article published in the journal Development (Irie et al., Retrovirus-derived RTL5 and RTL6 genes are novel constituents of the innate immune system in the eutherian brain).

The studied retrotransposons are present in all placental mammals and are very similar to the genes of modern retroviruses, which is why the assumption about the viral nature of these DNA sections arose. The researchers were sure that RTL5 and RTL6 should have a function important enough for mammals to be preserved in their genome for several tens of millions of years. To determine the functions of these genes, the authors of the study found out in which cells and under what circumstances these genes are active, as well as which proteins they encode. 

Using the example of mice, scientists have shown that RTL5 and RTL6 are actively expressed in brain microglia cells. These cells play an important role in the formation of neural networks of the brain, maintaining contacts between neurons and fighting pathogens that for some reason have overcome the blood-brain barrier. 


RTL6 proteins, shown in green, protect the capillaries of the mouse brain (branched structures highlighted in black) from "infection" by grouping around purple bacterial imitations.

Moreover, microglia with active RTL5 reacted to viral infection, whereas the activity of RTL6 allowed microglia cells to fight bacterial infection.

Moreover, the removal of these genes made microglial cells helpless against viral and bacterial infections, which indicates the crucial role of retrotransposons in maintaining the sterility of the brain of placental mammals, including humans. In the future, the authors of the article suggest paying more attention to the genes of primates and humans acquired from retroviruses in order, perhaps, to better understand our evolution.

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