The Mutation Behind The Delta Variant’s Severity

A mutation in the spike protein enhances the Delta variant’s ability to fuse with host cells, resulting in more severe COVID-19 symptoms.

AsianScientist (Nov 29, 2021) – From Alpha to Beta and now Omicron, we’re all probably a little more familiar with the Greek alphabet than we ever have been, thanks to the SARS-CoV-2 variants that have cropped up in the months since the COVID-19 pandemic seized the world.

Of all the variants identified, the B.1.617.2 or Delta variant, led to the most concern. People infected with the Delta variant suffered more severe symptoms and were more likely to require hospitalization than those infected with other variants of the virus. Worryingly, the Delta variant also appeared to be more contagious than previous variants, leading to surges in COVID-19 cases in multiple countries.

However, it was unclear exactly what was making the Delta variant behave this way.

Now, researchers from Japan may have identified a reason for the Delta variant’s severity: a mutation in the spike protein that enhances the virus’ ability to fuse with host cells and results in more severe symptoms than the original SARS-CoV-2 virus.

Led by University of Tokyo Associate Professor Sato Kei, the researchers analyzed the genomes of SARS-CoV-2 variants from the B.1.617 lineage, of which the Delta variant is a part, and identified a mutation that is highly conserved in the lineage.

The mutation, named P681R, is unique to the lineage and is located close to the furin cleavage site of the spike protein, an area that is important for fusion with and entry into host cells.

To test how the mutation affected the virus, the researchers generated an artificial virus bearing the same P681R mutation and subjected it to virological experiments testing its growth and fusion ability. The findings confirmed it displayed the same increased cell fusion ability as the Delta variant virus in a laboratory setting.

“These data suggest that the P681R mutation enhances and accelerates SARS-CoV-2 S-mediated fusion,” wrote the researchers.

Increased fusion ability is associated with more severe disease in some other viruses like HIV-1 encephalitis and measles.

Likewise in this study, Sato and his colleagues found that hamsters infected with the P681R-bearing virus displayed the same disease progression patterns as those infected with the Delta variant: both groups lost more weight and suffered worse pulmonary symptoms than hamsters infected with other strains and viruses without the mutation.

According to the researchers, the increased fusion ability conferred by the mutation could play a role in the Delta variant’s more severe effects on the body.

“Our data suggest that the P681R mutation is a hallmark of the virological phenotype of the B.1.617.2/Delta variant,” they wrote. “These findings suggest that enhanced viral fusogenicity, which is triggered by the P681R mutation, is closely associated with viral pathogenicity.”

The researchers further hypothesize that a similar approach to identify and test mutations unique to the Delta variant could help explain why it is so contagious.

The article can be found at: Saito et al. (2021) Enhanced fusogenicity and pathogenicity of SARS-CoV-2 Delta P681R mutation.


Source: University of Tokyo; Photo: Shutterstock.
Disclaimer: This article does not necessarily reflect the views of AsianScientist or its staff.

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