SARS-CoV-2-infected individuals could have different variants hidden in different parts of the body
New research shows virus plays ultimate game of `hide and seek' with
immune system

Date:
March 1, 2022
Source:
University of Bristol
Summary:
People suffering from COVID-19 could have several different
SARS-CoV- 2 variants hidden away from the immune system in different
parts of the body, finds new research. The study's authors say
that this may make complete clearance of the virus from the body
of an infected person, by their own antibodies, or by therapeutic
antibody treatments, much more difficult.



FULL STORY ========================================================================== People suffering from COVID-19 could have several different SARS-CoV-2
variants hidden away from the immune system in different parts of
the body, finds new research published in Nature Communications by an international research team.

The study's authors say that this may make complete clearance of the
virus from the body of an infected person, by their own antibodies,
or by therapeutic antibody treatments, much more difficult.


========================================================================== COVID-19 continues to sweep the globe causing hospitalisations and deaths, damaging communities and economies worldwide. Successive variants of
concern (VoC), replaced the original virus from Wuhan, increasingly
escaping immune protection offered by vaccination or antibody treatments.

In new research, comprising two studies published in parallel in Nature Communications, an international team led by Professor Imre Berger at
the University of Bristol and Professor Joachim Spatz at the Max Planck Institute for Medical Research in Heidelberg , both Directors of the Max
Planck Bristol Centre of Minimal Biology, show how the virus can evolve distinctly in different cell types, and adapt its immunity, in the same infected host.

The team sought to investigate the function of a tailor-made pocket in
the SARS-CoV-2 spike protein in the infection cycle of the virus. The
pocket, discovered by the Bristol team in an earlier breakthrough,
played an essential role in viral infectivity.

"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." Intriguingly, BrisDelta, presents as a small subpopulation in the samples taken from patients, but appears to infect certain cell-types better than the virus
that dominated the first wave of infections.

Dr Kapil Gupta, lead author of the BrisDelta study, explains: "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." The team applied cutting-edge synthetic biology techniques, state-of-the-art imaging and cloud computing to decipher
viral mechanisms at work. To understand the function of the pocket,
the scientists built synthetic SARS-CoV-2 virions in the test tube,
that are mimics of the virus but have a major advantage in that they
are safe, as they do not multiply in human cells.

Using these artificial virions, they were able to study the exact
mechanism of the pocket in viral infection. They demonstrated that upon
binding of a fatty acid, the spike protein decorating the virions changed
their shape. This switching 'shape' mechanism effectively cloaks the
virus from the immune system.

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,
explains: "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." "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." Halo Therapeutics, a recent University of Bristol spin-out founded by the
authors, pursues exactly this approach to develop pocket-binding pan- coronavirus antivirals.

The team included experts from Bristol UNCOVER Group, the Max Planck
Institute for Medical Research in Heidelberg, Germany, Bristol University spin-out Halo Therapeutics Ltd and further collaborators in UK and
in Germany. The studies were supported by funds from the Max Planck Gesellschaft, the Wellcome Trust and the European Research Council,
with additional support from Oracle for Research for high-performance
cloud computing resources. The authors are grateful for the generous
support by the Elizabeth Blackwell Institute of the University of Bristol.

========================================================================== Story Source: Materials provided by University_of_Bristol. Note: Content
may be edited for style and length.


========================================================================== Journal References:
1. Kapil Gupta, Christine Toelzer, Maia Kavanagh Williamson, Deborah K.

Shoemark, A. Sofia F. Oliveira, David A. Matthews, Abdulaziz
Almuqrin, Oskar Staufer, Sathish K. N. Yadav, Ufuk Borucu,
Frederic Garzoni, Daniel Fitzgerald, Joachim Spatz, Adrian
J. Mulholland, Andrew D. Davidson, Christiane Schaffitzel, Imre
Berger. Structural insights in cell-type specific evolution of
intra-host diversity by SARS-CoV-2. Nature Communications, 2022;
13 (1) DOI: 10.1038/s41467-021-27881-6
2. Oskar Staufer, Kapil Gupta, Jochen Estebano Hernandez Bu"cher,
Fabian
Kohler, Christian Sigl, Gunjita Singh, Kate Vasileiou, Ana
Yagu"e Relimpio, Meline Macher, Sebastian Fabritz, Hendrik Dietz,
Elisabetta Ada Cavalcanti Adam, Christiane Schaffitzel, Alessia
Ruggieri, Ilia Platzman, Imre Berger, Joachim P. Spatz. Synthetic
virions reveal fatty acid- coupled adaptive immunogenicity of
SARS-CoV-2 spike glycoprotein. Nature Communications, 2022; 13
(1) DOI: 10.1038/s41467-022-28446-x
3. Christine Toelzer, Kapil Gupta, Sathish K. N. Yadav, Ufuk Borucu,
Andrew
D. Davidson, Maia Kavanagh Williamson, Deborah K. Shoemark, Frederic
Garzoni, Oskar Staufer, Rachel Milligan, Julien Capin, Adrian J.

Mulholland, Joachim Spatz, Daniel Fitzgerald, Imre Berger,
Christiane Schaffitzel. Free fatty acid binding pocket in the
locked structure of SARS-CoV-2 spike protein. Science, 2020; 370
(6517): 725 DOI: 10.1126/ science.abd3255 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2022/03/220301131121.htm

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