All about cheaters
Scientists have figured out how viruses deceive an infected cell
A team of scientists from Moscow State University, the Institute of Protein of the Russian Academy of Sciences and other organizations has published a large review of unusual techniques by which viruses force an infected cell to synthesize its proteins instead of those that it needs itself. The article was published in the anniversary collection of the journal "Biochemistry", dedicated to the memory of Academician Alexander Sergeevich Spirin.
Our planet is populated by viruses, many of which pose a danger to human health and life. Viruses are molecular parasites, they not only use the resources of an infected cell, but also "rent" many of its parts and mechanisms, producing thousands of new viral particles instead of paying.
Viruses are different – some of them have such a large genome that almost all the components necessary for primitive cellular life could be encoded in it. However, there is a mechanism, the details of which, apparently, are never presented in their complete set - this is a translational apparatus necessary for protein biosynthesis. Its central component is the ribosome, a complex molecular machine consisting of a large number of diverse parts, ribosomal RNAs and proteins. Perhaps the point here is that the assembly of this machine is so complicated, requires such a huge amount of energy and the coordinated work of such a large number of genes that it is simply impractical to "carry it all with you": it is much easier to use a ready-made one. However, this makes viruses completely dependent on the cellular translational apparatus, and in order to ensure the synthesis of their proteins, viruses have to compete with matrix RNAs (mRNAs) encoding proteins of the cell itself.
"This is where viruses have to use numerous tricks," says Ivan Sorokin, a junior researcher at the Belozersky Research Institute of the Moscow State University, a co-author of the article. – For example, at one of the ends of cellular mRNAs, to which the ribosome usually binds, there is a special chemical structure called a "cap". One of the main functions of the cap is that special cellular proteins (cap-binding factors) bind to it, which then attract the ribosome and thus contribute to the beginning (initiation) of translation. So, the mRNAs of many viruses do not have a cap, but in the course of evolution they have learned to turn this disadvantage into an advantage. Thus, the polio virus encodes a special enzyme – a protease that cuts the cap-binding protein of the cell. It immediately "takes out of the game" cellular mRNAs. At the same time, the RNA of the virus itself contains a special section (IRES) that binds the "pruning" of this factor – thanks to this, the viral mRNA continues to be translated as if nothing had happened."
In some viruses, a small viral protein (VPg) is located at the end instead of the cap, which binds the same factors as the cap. And many plant viruses have special signals (3’ CITE) at the opposite end of the mRNA, but thanks to the closure of the mRNA molecule into the ring, they also manage to attract the ribosome to the right place. "But the notorious coronavirus SARS-CoV-2, which caused the current COVID-19 pandemic, uses a completely different "technique," Ivan continues. – It encodes a protein that "plugs" the ribosome like a cork and prevents it from binding to cellular mRNAs. At the same time, all the mRNAs of the coronavirus itself contain a special structure that is able to displace the "plug" during their translation. And there are many such tricks. Here we are considering them in our review."
"Protein biosynthesis is the Achilles heel of viruses, since a healthy cell usually does not need to synthesize protein in such large quantities as with a viral infection," continues another co–author, head of the Department of virus–cell interaction at the Belozersky Research Institute of the Moscow State University Sergey Dmitriev. – Many low-molecular-weight substances that suppress translation may turn out to be potential broad-spectrum antiviral drugs. And understanding such specific translation mechanisms, which we consider in our review, can help in the fight against specific viral infections. However, our review had another goal. By writing it, we wanted to pay tribute to the memory of Academician Spirin, a remarkable scientist who made a huge contribution to the study of protein biosynthesis and was also engaged in research on the translation of viral mRNAs. Our team includes students and friends of Alexander Sergeevich, his colleagues, co-authors and employees who worked with him at the Institute of Protein of the Russian Academy of Sciences, at the Faculty of Biology and at the Research Institute of the Moscow State University."
The review was published in two versions – in Russian and in English. On the official website of the journal "Biochemistry" you can find other interesting articles that made up two anniversary issues, which were published in August and September. The work was supported by a grant from the Russian Science Foundation.
Information provided by the MSU press service
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