Cellular signalling by SARS-CoV-2 spike protein

Nicholas P. Gracie; Lachlan Y. S. Lai; Timothy P. Newsome

doi:10.1071/MA24005

RESEARCH ARTICLE (Open Access)

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Cellular signalling by SARS-CoV-2 spike protein

Nicholas P. Gracie

^A ^# , Lachlan Y. S. Lai

^A ^# and Timothy P. Newsome

^A ^B ^*

+ Author Affiliations

- Author Affiliations

^A School of Life and Environmental Sciences, The University of Sydney, Camperdown, Sydney, NSW, Australia.

^B Sydney Institute for Infectious Diseases (Sydney ID), The University of Sydney, Camperdown, Sydney, NSW, Australia.

Nicholas Gracie is a 3rd Year PhD candidate in the Newsome Lab at The University of Sydney. His research involves poxviruses, SARS-CoV-2 and cell signalling.

Lachlan Lai is a 1st Year PhD candidate in the Newsome Lab at The University of Sydney. His research involves poxviruses with a focus on Monkeypox.

Timothy Newsome is an Associate Professor of The University of Sydney. His research interests lie at the intersection of virology and cell signalling.

^* Correspondence to: timothy.newsome@sydney.edu.au

^# These authors contributed equally to this paper

Microbiology Australia 45(1) 13-17 https://doi.org/10.1071/MA24005

Submitted: 18 January 2024 Accepted: 7 March 2024 Published: 22 March 2024

© 2024 The Author(s) (or their employer(s)). Published by CSIRO Publishing on behalf of the ASM. This is an open access article distributed under the Creative Commons Attribution 4.0 International License (CC BY)

Abstract

Following the release of the SARS-CoV-2 genome, the spike protein was identified as the key viral protein mediating cell entry. In addition to its critical function in delivering the viral genome to the host cytoplasm, the spike protein is able to activate diverse cell signalling pathways, leading to notable cellular responses, including inflammation, cellular remodelling, and immune evasion. The spike protein is associated with the induction of a ‘cytokine storm’ characterised by elevated levels of proinflammatory cytokines like IL-6 and IL-1β. Moreover, the spike protein deregulates TGF-β and E-selectin, leading to fibrotic injury and tissue scarring in cellular remodelling, notably in pulmonary tissues. Finally, the spike protein plays a role in immune evasion, disrupting Type I interferon responses. Understanding these diverse interactions and effects is crucial for comprehending the pathogenesis of COVID-19 and developing effective therapeutic strategies.

Keywords: ACE2, Angiotensin Converting Enzyme Receptor 2, cellular signalling, COVID-19, cytokine storm, fibrosis, spike protein, TGF-β, transforming growth factor-beta.

Biographies

Nicholas Gracie is a 3rd Year PhD candidate in the Newsome Lab at The University of Sydney. His research involves poxviruses, SARS-CoV-2 and cell signalling.

Lachlan Lai is a 1st Year PhD candidate in the Newsome Lab at The University of Sydney. His research involves poxviruses with a focus on Monkeypox.

Timothy Newsome is an Associate Professor of The University of Sydney. His research interests lie at the intersection of virology and cell signalling.

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