19 November 2020

How viruses search for new hosts

Viruses, including SARS-CoV-2, can quickly "rebuild" to other hosts due to overlapping genes?

"First-hand science"

Recently, a group of scientists from the USA, Germany and Taiwan discovered a so-called overlapping gene in the genome of the SARS-CoV-2 coronavirus, which may be responsible for its interspecific spread.

Article by Nelson et al. Dynamically evolving novel overlapping gene as a factor in the SARS-CoV-2 pandemic is published in the journal eLife.

The COVID-19 pandemic forced us not only to ask topical questions about the treatment and prevention of a new infection, but also increased interest in more fundamental problems. For example, how do viruses that usually affect only animals become dangerous to humans? To understand this, you need to know how viral genomes are arranged and function, in which hereditary information is stored in the form of nucleic acids (DNA or RNA).

As you know, nucleic acids are organic polymers consisting of individual units–monomers. Such links are called nucleotides, and there are only four types of them: adenine (A), thymine (T), guanine (G) and cytosine (C) (uracil, U is used in RNA instead of thymine). These nucleotides are the "letters" of the genetic code, and hereditary information can be simplified in the form of a text in which "words" (genes) are sequentially arranged in the form of a certain set of nucleotides.

Genes are "recipes" for the production of various proteins, and each amino acid that is part of them is encoded by a triple of nucleotides. Usually genes are separated from each other by special nucleotide sequences, so that as a result they can only be "read" in a strictly defined way. This is how the principle of "one gene – one protein" is maintained.

But there is, mainly in viruses, such a rare phenomenon as overlapping genes. In this case, several genes are encoded on the same nucleotide sequence at once – it all depends on where to start "reading" them and where to finish them.

Scientists suggest that the presence of such "genes in the genes" in viruses is due to the fact that the viral genome is very short. For example, the same coronavirus SARS-CoV-2 has only 15 genes, despite the fact that he and his closest "relatives" have one of the longest RNA genomes. In addition, RNA viruses mutate quickly, and in this sense it is more profitable for them to have a smaller genome, in which there will be fewer mutations.

One way or another, viruses have developed a kind of data compression system in which each "letter"-a nucleotide can contribute to two or three different genes. Accordingly, even one mutation can change more than one protein at once. Knowledge about overlapping genes opens up new opportunities for the development of antiviral drugs. But here's the problem: overlapping genes are hard to detect, and most specialized computer programs aren't designed to find them.

Recently, a research team using a proprietary search algorithm aimed at identifying overlapping genes, discovered such a gene in the SARS-CoV-2 coronavirus. The gene, called ORF3d, could not be detected in other coronaviruses of bats, but it is available in the coronavirus of pangolins, which are considered intermediate hosts of SARS-CoV-2 on the way to humans. Probably, this fact could contribute to the crossing of the species barrier and determine the features of the spread of this virus.

Scientists, however, emphasize that the biological role of ORF3d is not yet very clear, although it is known that the protein it encodes causes a humoral immune response in COVID-19 patients with the production of specific antibodies. There is one caveat here: previously, this SARS-CoV-2 gene was mistakenly classified as a long-known ORF3b gene, so only further ORF3d studies will more accurately characterize its biological role.

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