SARS-CoV-2 spike protein S1 activates Cx43 hemichannels and disturbs intracellular Ca2+ dynamics

Biological Research

Research Article

Maximiliano Rovegno¹  Juan A. Orellana²  Juan Prieto-Villalobos²  Claudia M. Lucero³  Gonzalo I. Gómez³  Mauricio A. Retamal⁴ 

[1] Departamento de Medicina Intensiva, Facultad de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile;Departamento de Neurología, Escuela de Medicina and Centro Interdisciplinario de Neurociencias, Facultad de Medicina, Pontificia Universidad Católica de Chile, Marcoleta 391, Santiago, Chile;Institute of Biomedical Sciences, Faculty of Health Sciences, Universidad Autónoma de Chile, Santiago, Chile;Programa de Comunicación Celular en Cancer, Facultad de Medicina Clínica Alemana, Universidad del Desarrollo, Santiago, Chile;

关键词: Hemichannels;    COVID-19;    Connexin 43;    SARS-CoV-2;    ACE2;    ATP and spike S1;   

DOI  :  10.1186/s40659-023-00468-9

 received in 2023-06-14, accepted in 2023-10-12,  发布年份 2023

来源: Springer

【 摘 要 】

BackgroundSevere 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.ResultsWe 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 [Ca2+]i dynamics elicited by ATP.ConclusionsWe hypothesize that Cx43 hemichannels could represent potential pharmacological targets for developing therapies to counteract SARS-CoV-2 infection and their long-term consequences.

【 授权许可】

CC BY   
© Sociedad de Biologia de Chile 2023

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