An unsuspected weapon against the coronavirus? After two years of the pandemic, we have learned how our immune system activates to stop the virus and prevent it from causing harm, a defense that proves effective in most infected people. However, a new component of this immune defense has just been unveiled, a mechanism which prevents the virus from replicating… but which could also accelerate its evolution. A Swedish study published on February 8, 2022 in the journal PNAS showed that the infection leads to the activation of an enzyme, called ADAR1 (for “adenosine deaminase acting on RNA”), which causes mutations in the RNA of the virus. Study leader Prof. Michael Kann of the University of Gothenburg told Science and Future this amazing discovery.
A defense against RNA viruses like the coronavirus
“ADAR1 is not very well known, it is an enzyme that is part of the innate immune system, which targets RNA and produces mutations there, summarizes Michael Kann. It modifies adenosines (A) into inosines, and during RNA replication this modification causes a copy error and these inosines are read as guanosines (G), so A becomes G.” The researchers studied nearly 300,000 sequences of the coronavirus, showing that this mutation (A to G) was much more frequent than all the other mutations, which highlighted the activation of ADAR1. But what could be the use of these modifications made by this enzyme?
“In the majority of cases, these mutations are negative for the virus and we see a correlation between the number of these mutations and a drop in the viral load., he replies. The hypothesis is therefore that this enzyme generates an accumulation of mutations in the RNA of the virus, leading to chain errors which end up preventing the replication of the virus, thus stopping the infection and therefore reducing the viral load (i.e. i.e. the number of viral particles). Kann and his team do not yet know the exact mechanism by which this enzyme is activated, but pursue an interesting lead: “We see a correlation between the activity of this enzyme and inflammation, so ADAR1 is probably expressed following an inflammatory state”, adds the virologist.
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A defense that could prove harmful?
Since the function of ADAR1 is to modify RNA, is it possible that it also targets the RNA molecules of our cells? “Potentially, ADAR1 could also cause changes in the RNA of our cells, but that probably wouldn’t have much impact. This modification of adenosine to inosine in the messenger RNA risks blocking the ribosome and causing a long pause in translation, but there are many copies of these mRNA molecules so the modification of a few of them should not have significant consequences”, reassures us Michael Kann.
On the other hand, these mutations could be harmful not by targeting our RNA, but by accelerating the evolution of the virus and thus leading to the emergence of variants. “In theory, it is possible that this accelerates the evolution of the virus, but only mutations that are disadvantageous for the virus have been found, the vast majority of which affect replication.he replies. This possibility is currently being analyzed, investigating whether ADAR1 could be responsible for some of the mutations found in the coronavirus variants of concern. But for the moment we have not found any evidence in this direction..” This enzyme would therefore be a weapon against the coronavirus and not against ourselves, until proven otherwise.
With Science to come
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