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How do viruses like COVID19 increase their genetic diversity?

Niti Post - March 21, 2023
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Viruses like SARS-CoV-2 are known to change constantly, making it hard for the immune system of human bodies to identify and destroy them. This also becomes a major roadblock while generating vaccines.

In January 2022, around the time when the Omicron variant of SARS-CoV-2 started spreading rapidly, a team of researchers at the Indian Institute of Science (IISc) headed by Shashank Tripathi, Assistant Professor at the Department of Microbiology & Cell Biology, and Centre for Infectious Diseases Research, noticed that there was an unusually high increase in the number of recombinant strains of the Omicron variant. 

Can these new variants cause severe infections?

The team analysed genomic sequences of all the viral strains that appeared between November 2019 and July 2022 in various databases worldwide. In this study, the researchers identified several new mutations that accumulated through recombination at a high rate and affected viral proteins, especially different parts (domains) of the viral spike protein.

These domains – such as the Receptor Binding Domain (RBD) and N Terminal Domain (NTD) – are known to be involved in the virus-host binding and have also been reported as sites of attack by the host’s immune system. The study notes that, with the aid of these mutations, several such Omicron recombinant and mutant strains were able to escape from the host’s defences and bind more tightly to the host cell.

The genetic material in SARS-CoV-2 is a long single-stranded RNA. Moreover, the protein that is required to make copies of this RNA – RNA polymerase – is known to be error-prone in this virus. 

These observations noted by the team add to growing evidence about how efficient new strains of the virus are at escaping immune attacks and at causing infections.

How do viruses evolve?

Prof. Tripathi explains that Viruses can evolve via one of two mechanisms: mutation or recombination. “This is a strategy to increase its genetic diversity,” he notes.

The polymerase (an enzyme that synthesizes long chains of polymers or nucleic acids) doesn’t just allow mutations to accumulate, it often also causes recombination to happen between different strains of the virus. This is possible when there is co-infection – when a host cell is infected by more than one strain of the virus.

“When copying the viral RNA, the polymerase can jump from one RNA template to another that is nearby,” elaborates Prof. Tripathi. If the nearby sequence is that of another strain, then the new copy will be a recombinant or a hybrid of the two parental strains. “There are currently more than 35 recombinants of SARS-CoV-2,” the Professor informs giving the example of XBB, one of the more efficient variants, which emerged in 2022 and was born from the recombination between two other versions of Omicron. 

The Study further explains two possible reasons for the increase in these recombination events. First, the number of infections and co-infections was high during the 2022 Omicron wave. Second, the team noticed that a specific mutation has appeared in a viral gene for an exonuclease, a protein that can cleave RNA and is believed to be involved in recombination.

The Research show that the virus is not cooling down but is actually warming up as far as mutations go. Since enhanced recombination can increase the chances of new strains emerging, tracking such recombinations through regular sequencing of the virus is pivotal to understanding the genetic diversity of viruses

 

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