SARS-CoV-2 spike protein S1 activates Cx43 hemichannels and disturbs intracellular Ca2+ dynamics
Journal
Biological Research
ISSN
0717-6287
Date Issued
2023
Author(s)
Juan Prieto-Villalobos
Claudia M. Lucero
Maximiliano Rovegno
Gonzalo I. Gómez
Juan A. Orellana
Type
Resource Types::text::journal::journal article
URL Institutional Repository
Abstract
<jats:title>Abstract</jats:title><jats:sec>
<jats:title>Background</jats:title>
<jats:p>Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes the ongoing coronavirus disease 2019 (COVID-19). An aspect of high uncertainty is whether the SARS-CoV-2 per se or the systemic inflammation induced by viral infection directly affects cellular function and survival in different tissues. It has been postulated that tissue dysfunction and damage observed in COVID-19 patients may rely on the direct effects of SARS-CoV-2 viral proteins. Previous evidence indicates that the human immunodeficiency virus and its envelope protein gp120 increase the activity of connexin 43 (Cx43) hemichannels with negative repercussions for cellular function and survival. Here, we evaluated whether the spike protein S1 of SARS-CoV-2 could impact the activity of Cx43 hemichannels.</jats:p>
</jats:sec><jats:sec>
<jats:title>Results</jats:title>
<jats:p>We found that spike S1 time and dose-dependently increased the activity of Cx43 hemichannels in HeLa-Cx43 cells, as measured by dye uptake experiments. These responses were potentiated when the angiotensin-converting enzyme 2 (ACE2) was expressed in HeLa-Cx43 cells. Patch clamp experiments revealed that spike S1 increased unitary current events with conductances compatible with Cx43 hemichannels. In addition, Cx43 hemichannel opening evoked by spike S1 triggered the release of ATP and increased the [Ca<jats:sup>2+</jats:sup>]<jats:sub>i</jats:sub> dynamics elicited by ATP.</jats:p>
</jats:sec><jats:sec>
<jats:title>Conclusions</jats:title>
<jats:p>We hypothesize that Cx43 hemichannels could represent potential pharmacological targets for developing therapies to counteract SARS-CoV-2 infection and their long-term consequences.</jats:p>
</jats:sec>
<jats:title>Background</jats:title>
<jats:p>Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes the ongoing coronavirus disease 2019 (COVID-19). An aspect of high uncertainty is whether the SARS-CoV-2 per se or the systemic inflammation induced by viral infection directly affects cellular function and survival in different tissues. It has been postulated that tissue dysfunction and damage observed in COVID-19 patients may rely on the direct effects of SARS-CoV-2 viral proteins. Previous evidence indicates that the human immunodeficiency virus and its envelope protein gp120 increase the activity of connexin 43 (Cx43) hemichannels with negative repercussions for cellular function and survival. Here, we evaluated whether the spike protein S1 of SARS-CoV-2 could impact the activity of Cx43 hemichannels.</jats:p>
</jats:sec><jats:sec>
<jats:title>Results</jats:title>
<jats:p>We found that spike S1 time and dose-dependently increased the activity of Cx43 hemichannels in HeLa-Cx43 cells, as measured by dye uptake experiments. These responses were potentiated when the angiotensin-converting enzyme 2 (ACE2) was expressed in HeLa-Cx43 cells. Patch clamp experiments revealed that spike S1 increased unitary current events with conductances compatible with Cx43 hemichannels. In addition, Cx43 hemichannel opening evoked by spike S1 triggered the release of ATP and increased the [Ca<jats:sup>2+</jats:sup>]<jats:sub>i</jats:sub> dynamics elicited by ATP.</jats:p>
</jats:sec><jats:sec>
<jats:title>Conclusions</jats:title>
<jats:p>We hypothesize that Cx43 hemichannels could represent potential pharmacological targets for developing therapies to counteract SARS-CoV-2 infection and their long-term consequences.</jats:p>
</jats:sec>
Cite this document
Prieto-Villalobos, J., Lucero, C. M., Rovegno, M., Gómez, G. I., Retamal, M. A., & Orellana, J. A. (2023). SARS-CoV-2 spike protein S1 activates Cx43 hemichannels and disturbs intracellular Ca2+ dynamics. Biological Research, 56(1), 56. https://doi.org/10.1186/s40659-023-00468-9
Subjects
ace2
;
atp and spike s1
;
connexin 43
;
covid-19
;
hemichannels
;
sars-cov-2
;
adenosine triphosphate
;
connexin 43
;
covid-19
;
humans
;
sars-cov-2
;
spike glycoprotein, coronavirus
;
adenosine triphosphate
;
connexin 43
;
coronavirus spike glycoprotein
;
spike protein, sars-cov-2
;
coronavirus disease 2019
;
human
;
severe acute respiratory syndrome coronavirus 2