A new study in Nature Communications says that people who have COVID-19 may have several different SARS-CoV-2 variants that aren’t visible to the immune system in different parts of their bodies, which could make them more vulnerable to the virus.
According to the study’s authors, this may make completely removing the virus from an infected person’s body, either by their own antibodies or through therapeutic antibody therapy, considerably more challenging.
COVID-19 is still sweeping the globe, causing hospitalizations and fatalities and wreaking havoc on communities and economies around the world. Variants of concern (VoC) have gradually supplanted the original Wuhan virus, eluding immunological protection provided by vaccination or antibody therapies.
Two new studies published parallelly in Nature Communications demonstrate how the virus can evolve uniquely in different cell types and adapt its immunity within the same infected host.
The researchers wanted to know how a custom-made pocket in the SARS-CoV-2 spike protein affects the virus’s infection cycle. The pocket, which was uncovered by the Bristol researchers in a previous breakthrough, was critical for viral infectivity.
“An incessant series of variants have completely replaced the original virus by now, with Omicron and Omicron 2 dominating worldwide,” says Professor Imre Berger. “We analyzed an early variant discovered in Bristol, BrisDelta. It had changed its shape from the original virus, but the pocket we had discovered was there, unaltered.”
Surprisingly, BrisDelta appears to infect some cell types better than the virus that dominated the first wave of infections, despite being a minor subpopulation of inpatient data.
Dr. Kapil Gupta, the lead author of the study, says: “Our results showed that one can have several different virus variants in one’s body. Some of these variants may use kidney or spleen cells as their niche to hide, while the body is busy defending against the dominant virus type. This could make it difficult for the infected patients to get rid of SARS-CoV-2 entirely.”
To identify viral mechanisms at work, the scientists used cutting-edge synthetic biology approaches, cutting-edge imaging, and cloud computing. To figure out how the pocket works, scientists created synthetic SARS-CoV-2 virions in a test tube that are virus-like but harmless because they don’t grow in human cells.
They were able to analyze the exact mechanism of the pocket in viral infection using these fake virions. They showed that when a fatty acid was bound, the spike protein that adorned the virions changed shape. This changing “shape” mechanism hides the virus from the body’s defenses.
“By ‘ducking down’ of the spike protein upon binding of inflammatory fatty acids, the virus becomes less visible to the immune system,” highlights lead author of the study Dr. Oskar Staufer, adding, “this could be a mechanism to avoid detection by the host and a strong immune response for a longer period of time and increase total infection efficiency.”
“It appears that this pocket, specifically built to recognize these fatty acids, gives SARS-CoV-2 an advantage inside the body of infected people, allowing it to multiply so fast. This could explain why it is there, in all variants, including Omicron” adds Professor Berger.
“Intriguingly, the same feature also provides us with a unique opportunity to defeat the virus, exactly because it is so conserved—with a tailormade antiviral molecule that blocks the pocket.”
Source: 10.1038/s41467-022-28446-x
Image Credit: Getty
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