Research finds mutations in SARS-CoV-2 variants that increase infection

Photo of a covid particle
Ytoyoda/Creative Commons
Researchers working for UC Berkeley's Innovative Genomics Institute and Gladstone Institutes find that mutations in the nucleocapsid protein increases the virus' transmissibility and infectivity. Photo by Ytoyoda under CC BY 2.0.

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Researchers from UC Berkeley and Gladstone Institutes identified why some variants of SARS-CoV-2, the virus that causes COVID-19, lead to increased transmission and infectivity in a study published Nov. 4.

The study was a collaboration between UC Berkeley’s Innovative Genomics Institute, or IGI, and Gladstone Institutes. Using an innovative method of studying viral particles, the researchers found that mutations in the nucleocapsid protein of the SARS-CoV-2 variants play an important role in higher transmission rates, according to Melanie Ott, director of the Gladstone Institute of Virology and co-author of the study.

“Variants, like the Delta variant, have small changes in the virus’ genetic code, leading to slightly different versions of key proteins,” said Abdullah Syed, a postdoctoral fellow at the Gladstone Institutes and co-first author of the study, in an IGI press release. “We were especially interested in looking at whether there were any changes to the genetic code that improved the efficiency of the assembly process for the virus and if that could be affecting infectivity.”

According to Syed, the researchers used virus-like particles, or VLPs, to analyze mutations in the variants. This method simulates real virus particles by expressing only four out of 26 proteins in the virus. These VLPs do not have the genome that makes them infectious, which enables researchers to safely work with them in a lab, added Taha Taha, a postdoctoral scholar at the Gladstone Institute of Virology, in the press release.

Syed noted that the use of VLPs also allowed the researchers to test mutations of proteins in the virus quickly.

The researchers made mutations to two proteins of the VLPs called the spike and nucleocapsid proteins. They discovered that mutations of the nucleocapsid protein increased the amount of RNA packaged in the particle, which is what makes the particle viral, by nearly tenfold, according to Syed.

Syed added in the press release that these mutations correlate with increased rates of spread of the delta COVID-19 variant.

“This matches what has been observed in people infected with the delta variant in that they produce 10 times more virus in their nose and throat compared to people infected with the older variants,” Syed said in the press release.

To verify that the patterns found in VLPs corresponded to the behavior of the actual virus, Takako Tabata, a postdoctoral scholar at the Gladstone Institute of Virology, worked directly with cells of the delta variant and SARS-CoV-2 variants, according to the press release. Tabata noted that the mutations of the nucleocapsid protein did indeed increase the virus’ transmissibility and infectivity, matching the earlier VLPs results.

According to Syed, a key finding of the study was the usefulness of VLPs to study viral particles and identify how mutations can change their behavior. He added that this method can help inform scientists when developing drugs to fight a virus.

“VLPs make it possible to study viral assembly and examine whether mutations, drugs, or different structural proteins change the efficiency of assembly,” Syed said in an email. “We can also use this system to study viruses that have not jumped to humans yet and see if they are capable of assembling in human cells.”

Amudha Sairam is a research and ideas reporter. Contact her at [email protected] and follow her on Twitter at @AmudhaSairam.