People with COVID-19 may have different variants in different parts of the body, according to two studies published in Nature Communications (1,2). The authors say this could make complete clearance of the virus much more difficult to achieve.
An international team of researchers led by Professor Imre Berger at the University of Bristol and Professor Joachim Spatz at the Max Planck Institute for Medical Research in Heidelberg showed how the virus can evolve separately in different cell types in the same infected host. This work builds on a previous study by the Bristol team, where they uncovered a “pocket” in the SARS-CoV-2 spike Protein, which plays a vital role in determining how the virus infects our cells.
“An incessant series of variants have completely replaced the original virus by now, with Omicron and Omicron 2 dominating worldwide,” said Professor Imre Berger. “We analysed 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”.
Curiously, the new BrisDelta variant appears in a small group of people but seems to infect some types of cells 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. 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,” said Dr. Kapil Gupta, lead author of the BrisDelta study.
The team used synthetic biology and imaging techniques to unveil how the virus works during infection. To understand how this pocket is involved, the researchers built synthetic versions of SARS-CoV-2 and created different conditions in a test tube. It turns out that when this pocket recognises fatty acids, it allows the virus to bind and change the spike protein in such a way that the immune system can no longer detect it.
“By ‘ducking down’ of the spike protein upon binding of inflammatory fatty acids, the virus becomes less visible to the immune system. 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,” said Dr. Oskar Staufer, lead author of this study and joint member of the Max Planck Institute in Heidelberg and the Max Planck Centre in Bristol.
“It appears that this pocket, specifically built to recognise 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,” added 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.”
(1) Gupta, K., Toelzer, C., Williamson, M.K. et al. Structural insights in cell-type specific evolution of intra-host diversity by SARS-CoV-2. Nat Commun 13, 222 (2022). https://doi.org/10.1038/s41467-021-27881-6
(2) Staufer, O., Gupta, K., Hernandez Bücher, J.E. et al. Synthetic virions reveal fatty acid-coupled adaptive immunogenicity of SARS-CoV-2 spike glycoprotein. Nat Commun 13, 868 (2022). https://doi.org/10.1038/s41467-022-28446-x
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