New clues to how SARS-CoV-2 infects cells
Date:
February 8, 2021
Source:
Uppsala University
Summary:
The molecular details of how SARS-CoV-2 enters cells and infects
them are still not clear. Researchers have identified receptors
that could be important players in the process.
FULL STORY ==========================================================================
The molecular details of how SARS-CoV-2 enters cells and infects them
are still not clear. Researchers at Uppsala University have tested
the bioinformatic predictions made by another research group and have identified receptors that could be important players in the process. The results are presented in the journal Science Signaling and at the AAAS
Annual Meeting held this week.
==========================================================================
The spike protein of SARS-CoV-2 binds the protein ACE2 on the outside
of the human cell. This triggers a series of events that leads to
invasion of the cell by the virus. The molecular details of this
process have remained obscure despite much research on SARS-CoV-2 and
other coronaviruses. Moreover, ACE2 is not present in human lung cells,
which would suggest that different players are involved when the virus
infects these cells.
A recent study by researchers at Uppsala University sheds some new light
on the issues. The study was published back-to-back with a study by
an international team led by Dr Toby Gibson at the European Molecular
Biology Laboratory (EMBL) in Heidelberg. The Gibson study predicted
potential interactions that could be of importance for the entry of
Sars-CoV-2 into the cell.
The researchers at Uppsala University tested the bioinformatic
predictions in vitro and could show that ACE2 and the potential
co-receptor integrin beta3 interact with important players involved in endocytosis and autophagy - cellular processes of uptake and disposal
of substances. This means that these processes might be hijacked by the
virus during infection.
"The Gibson team is world leading in terms of the bioinformatic analysis
of these types of interactions, and we were excited to follow up on
their predictions," says Professor Ylva Ivarsson, who headed the Uppsala
study. "Our results also helped them to improve their analysis. It was
an easy decision to engage in this project, as our lab has a strong
interest in host-pathogen protein-protein interactions."
========================================================================== Story Source: Materials provided by Uppsala_University. Note: Content
may be edited for style and length.
========================================================================== Journal References:
1. Johanna Kliche, Hanna Kuss, Muhammad Ali, Ylva Ivarsson. Cytoplasmic
short linear motifs in ACE2 and integrin b3 link SARS-CoV-2 host
cell receptors to mediators of endocytosis and autophagy. Science
Signaling, 2021; 14 (665): eabf1117 DOI: 10.1126/scisignal.abf1117
2. Ba'lint Me'sza'ros, Hugo Sa'mano-Sa'nchez, Jesu's Alvarado-Valverde,
Jelena Čalyseva, Elizabeth Marti'nez-Pe'rez, Renato Alves,
Denis C.
Shields, Manjeet Kumar, Friedrich Rippmann, Luci'a B. Chemes,
Toby J.
Gibson. Short linear motif candidates in the cell entry system used
by SARS-CoV-2 and their potential therapeutic implications. Science
Signaling, 2021; 14 (665): eabd0334 DOI: 10.1126/scisignal.abd0334 ==========================================================================
Link to news story:
https://www.sciencedaily.com/releases/2021/02/210208114246.htm
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