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Researchers Find Alpha Variant Uses Specific Protein To Evade Immune Response

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Researchers Find Alpha Variant Uses Specific Protein To Evade Immune Response

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New research into the development of the very first variant of the novel coronavirus has revealed that the Alpha variant developed mutations that suppressed specific aspects of the immune system, similar to mutations seen in newer variants such as Omicron.

The Alpha variant first appeared in the UK in the fall of 2020, introducing the world to the frightening idea of ​​variants of SARS-CoV-2, the virus that causes COVID-19. Although it has since been overtaken by later variants including Delta and Omicron, studying the structure and function of Alpha is helping scientists better understand how viral variants evolve.

Researchers from the US and UK worked together to study how Alpha attacked the human body and found that the mutations that allowed it to thrive go beyond those centered around the spike protein.

Their research, described in the journal Nature Thursday, found that the Alpha variant increased the production of a specific protein that could help suppress the way infected cells signaled to the immune system.

To learn more about how the Alpha variant works, the researchers looked at laboratory-grown cells infected with this variant to monitor protein levels and cell function.

They then compared the data to how cells responded to infection with the original strain of COVID-19. The biggest difference was in how the body’s innate immune response reacted – or not. This is the body’s first line of defense, which tries to keep pathogens out. Researchers say Alpha interfered with the rallying cry that typically activates this system.

Inside the cells infected with Alpha was an abundance of three viral proteins known to help COVID-19 bypass the immune response. One in particular, called Orf9b, has done this by blocking a protein in our cells that normally activates genes that signal our immune system to respond.

The researchers said in the study that this type of mutation could have helped improve the transmission of the Alpha variant by further suppressing this early immune response, which could have allowed the variant to replicate faster.

These results show that the spike protein isn’t the only factor researchers should think about when designing treatments to help people infected with COVID-19.

Because SARS-CoV-2 uses spike proteins on its surface to attach to receptors in a person’s cells, mutations around spike proteins are often more evoked than other types. With the Delta variant, a more efficient spike protein is believed to help it fuse better with our cells, and all current COVID-19 vaccines are targeted to cause our cells to produce immune responses against this spike protein.

“The mutations in the peak allow the virus to enter cells more efficiently,” Devan Krogan, one of the authors of the article and head of the Quantitative Biosciences Institute (QBI) at the University of California at San Francisco and his Coronavirus Research Group (QCRG), said in a press release.

“But what about after the virus gets into the cells? There may be other mutations that allow it to replicate further.

While each variant is different, many share similar mutations, with Delta and Omicron appearing as cousins ​​to the Alpha variant. Delta and Omicron both have similar mutations in the areas the researchers studied of the Alpha variant, meaning they could have similar impacts on the immune system.

“The virus will continue to evolve and adapt to the host, and each time it will adapt better and better,” Lorena Zuliani-Alvarez, co-author and senior scientist at QBI, said in the statement. . “That’s why Omicron has 53 mutations.”

The research points out that studying mutations outside of those around the spike protein will give scientists a broader picture of the virus as it evolves, which will be crucial in the fight against future variants.

“The study of the worrisome variants gives us ideas on the evolution of SARS-CoV-2,” Mehdi Bouhaddou, postdoctoral researcher and co-author, said in the statement. “Now we have an idea of ​​which proteins mutate most frequently and the biological consequences of those mutations. I think it helps us prepare for what might happen next. “

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