People infected with Covid may have different variants hidden in multiple body parts


People with Covid-19 may have several variants of the SARS-CoV-2 virus hidden from the immune system in different parts of the body, according to the results of two studies.

An international team led by researchers from the University of Bristol, UK, and the Max Planck Institute for Medical Research in Germany noted that this could make it much more difficult to completely eliminate the virus from the body of the infected person.

The studies, published in the journal Nature Communications, demonstrate how the virus can evolve distinctly in different cell types and adapt its immunity in the same infected host.

The researchers studied the function of a tailor-made pocket in the spike protein of SARS-CoV-2 in the infection cycle of the virus.

The pocket in the spike protein, which the virus uses to enter and infect cells, played a critical role in viral infectivity, they said. “A never-ending series of variants have completely replaced the original virus to date, with Omicron and Omicron 2 (a sub-variant) dominating worldwide,” said Professor Imre Berger from the University of Bristol.

“We analyzed an early variant discovered in Bristol, BrisDelta. It had changed shape from the original virus, but the pocket we discovered was there, unchanged,” Berger said.

The researchers noted that BrisDelta occurs as a small subpopulation in samples taken from patients, but appears to infect certain cell types better than the virus that dominated the first wave of infections.

“Our results showed that one can have several different virus variants in one’s body,” said Kapil Gupta, lead author of the BrisDelta study.

“Some of these variants can use kidney or spleen cells as a hiding place, while the body is busy defending itself against the dominant type of virus. This could make it difficult for infected patients to get rid of SARS-CoV-2 completely,” Gupta said.

The team applied state-of-the-art synthetic biology techniques, advanced imaging and cloud computing to decipher the viral mechanisms at work.

To understand the function of the pocket, the scientists constructed synthetic SARS-CoV-2 virions in the test tube, which are mimics of the virus but have a major advantage in that they are safe, as they do not not grow in human cells.

Thanks to these artificial virions, the researchers were able to study the exact mechanism of the pocket in the viral infection.

They demonstrated that upon binding of a fatty acid, the spike protein decorating the virions changed shape.

According to the researchers, this “shape” changing mechanism effectively masks the virus from the immune system.

“By ‘dodging’ the spike protein when binding inflammatory fatty acids, the virus becomes less visible to the immune system,” said Oskar Staufer, lead author of the second study. “This could be a mechanism to avoid host detection and a strong immune response for a longer period of time and increase the overall efficiency of infection,” Staufer said.

“It seems that this pocket, specially designed to recognize these fatty acids, gives SARS-CoV-2 an advantage inside the bodies of infected people, allowing it to multiply so quickly. That might explain why it’s there, in all variants, including Omicron,” Berger added.

However, the researchers noted that the same feature also provides a unique opportunity to defeat the virus, exactly because it is so conserved – with a bespoke antiviral molecule blocking the pocket.

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