Protective mutations in COVID-19

Date:
February 9, 2022
Source:
University of Gothenburg
Summary:
One way in which the body combats COVID-19 is by mutating the
coronavirus, making it less harmful. This built-in protective
mechanism in cells has a clear connection with decreased viral
load in the body, a new study shows.



FULL STORY ==========================================================================
One way in which the body combats COVID-19 is by mutating the coronavirus, making it less harmful. This built-in protective mechanism in cells has
a clear connection with decreased viral load in the body, a study from
the University of Gothenburg shows.


========================================================================== Mutations are often associated with the emergence of virus variants that
are more contagious and pathogenic than their predecessors. However,
the current study shows that virus mutations often work in the opposite direction.

Virology researchers at the University's Sahlgrenska Academy have mapped mutation patterns in the SARS-CoV-2 coronavirus. The results, published
in the journal PNAS, indicate that the body's natural enzyme ADAR1
(adenosine deaminases acting on RNA) impairs reproduction of SARS-CoV-2.

ADAR1, found inside the cells' protective membrane, can replace the nucleotides, which are the building blocks in the RNA of the virus.

Nevertheless, how ADAR1 affects the coronavirus causing COVID-19 it has
been unclear to date.

Mutations that benefit us "Our study shows that there is an inverse relationship between the viral load (the measurable amount of virus
in the body) and the extent to which ADAR1 has mutated the virus. We
also found that ADAR1-induced mutations are the most common type of
SARS-CoV-2 mutation," says Johan Ringlander, Ph.D. student in virology
at Sahlgrenska Academy and the study's first author.

In particular, the scientists noted that individual patients are often
infected with more than one variant of the virus. When mutations in
relatively rare virus variants were investigated, it was found that a
common mutation in which one nucleotide, guanosine (G), replaces adenosine
(A) significantly worsened the reproductive ability of SARS-CoV-2. These mutations are caused by the enzyme ADAR1.

Analyses of more than 200,000 virus strains from patients who were
ill with COVID-19 showed that mutations caused by ADAR1 were mainly
circulating in summer 2020, when transmission and mortality rates were
low in Europe. When transmission and mortality rates were higher, virus variants with ADAR1-induced mutations were uncommon, probably because
they were outcompeted by more infectious virus strains.

Helps to clear away "Our results clarify how the body's cells can generate mutated virus variants.

Mutations can make a virus more infectious, but in most cases the
mutations we've studied make the virus weaker; instead of spreading, it's removed from infected cells. These findings suggest that ADAR1 serves
as a protective mechanism used by the body to limit viral infections," Ringlander says.

Michael Kann, Professor of Clinical Virology at Sahlgrenska Academy and
chief physician at Sahlgrenska University Hospital, is the main author
of the article.

"When SARS-CoV-2 multiplies in the airways, inflammation occurs. Its
effects include activation of ADAR1, which in turn reduces the likelihood
of the virus infecting other cells. We're currently investigating whether
this protective mechanism may be important in other viral infections as
well," Kann says.

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


========================================================================== Journal Reference:
1. Johan Ringlander, Joshua Fingal, Hanna Kann, Kasthuri Prakash,
Gustaf
Rydell, Maria Andersson, Anna Martner, Magnus Lindh, Peter Horal,
Kristoffer Hellstrand, Michael Kann. Impact of ADAR-induced editing
of minor viral RNA populations on replication and transmission
of SARS-CoV- 2. Proceedings of the National Academy of Sciences,
2022; 119 (6): e2112663119 DOI: 10.1073/pnas.2112663119 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2022/02/220209093422.htm

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