An RGD motif on SARS-CoV-2 Spike induces TGF-β signaling and downregulates interferon

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) presents an ongoing public health challenge as a cause of acute illness and post-acute sequelae of COVID-19 (PASC, or long COVID). Our study identifies the RGD integrin-binding motif in the spike (S) protein as central to the cellular resp...

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Vydané v:	Journal of virology Ročník 99; číslo 9; s. e0043525
Hlavní autori:	Gracie, Nicholas P., Aggarwal, Anupriya, Luo, Rachel, Spicer, Mitchell, Idrees, Sobia, Ashley, Caroline L., Alca, Sibel, Ison, Timothy, Steain, Megan C., Patel, Karishma, Siddiquee, Rezwan, Low, Jason K. K., Mackay, Joel P., Denes, Christopher E., Neely, G. Gregory, Faiz, Alen, Turville, Stuart G., Newsome, Timothy P.
Médium:	Journal Article
Jazyk:	English
Vydavateľské údaje:	United States American Society for Microbiology 23.09.2025
Predmet:	Amino Acid Motifs Angiotensin-Converting Enzyme 2 - metabolism Animals coronavirus COVID-19 COVID-19 - metabolism COVID-19 - virology Down-Regulation Editor’s Pick HEK293 Cells Humans integrins Interferons - metabolism Oligopeptides - metabolism Plasminogen Activator Inhibitor 1 - genetics Plasminogen Activator Inhibitor 1 - metabolism RGD (Arg-Gly-Asp) SARS-CoV-2 SARS-CoV-2 - metabolism Signal Transduction Smad3 Protein - metabolism Spike Glycoprotein, Coronavirus - chemistry Spike Glycoprotein, Coronavirus - genetics Spike Glycoprotein, Coronavirus - metabolism TGF-β Transforming Growth Factor beta - metabolism Virology Virus-Cell Interactions COVID-19 SARS-CoV-2 integrins IFN-β RGD (Arg-Gly-Asp) PAI-1 TGF-β coronavirus
ISSN:	0022-538X, 1098-5514, 1098-5514
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Shrnutí:	Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) presents an ongoing public health challenge as a cause of acute illness and post-acute sequelae of COVID-19 (PASC, or long COVID). Our study identifies the RGD integrin-binding motif in the spike (S) protein as central to the cellular response to SARS-CoV-2, leading to the expression of the pleiotropic cytokine TGF-β and disabling of antiviral immunity. This work further supports the S protein-to-integrin complex signaling axis as a potential therapeutic target. The RGD motif might also be a valid target for treating PASC given the increasing body of evidence implicating the presence of persistent S protein in the etiology of this disease.
Bibliografia:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0022-538X 1098-5514 1098-5514
DOI:	10.1128/jvi.00435-25