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 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.
Authors
- Karishma Patel (ORCID: https://orcid.org/0000-0003-3034-3840)
- Alen Faiz (ORCID: https://orcid.org/0000-0003-1740-3538)
- G. Gregory Neely (ORCID: https://orcid.org/0000-0002-1957-9732)
- M.S. Spicer
- Caroline L. Ashley (ORCID: https://orcid.org/0000-0001-8355-8891)
- Jason K. K. Low (ORCID: https://orcid.org/0000-0003-0862-0012)
- Sibel Alca
- Megan Steain (ORCID: https://orcid.org/0000-0002-7631-4204)
- Christopher E. Denes (ORCID: https://orcid.org/0000-0002-8669-8088)
- Stuart Turville (ORCID: https://orcid.org/0000-0003-1918-5343)
- Timothy Ison
- Anupriya Aggarwal (ORCID: https://orcid.org/0000-0001-8678-0519)
- Joel P. Mackay (ORCID: https://orcid.org/0000-0001-7508-8033)
- Rezwan Siddiquee (ORCID: https://orcid.org/0000-0002-7893-3201)
- Sobia Idrees (ORCID: https://orcid.org/0000-0001-8512-7593)
- Timothy P. Newsome
- Nicholas P. Gracie (ORCID: https://orcid.org/0000-0001-9843-367X)
- Rachel Luo
Institutions
- University of Technology Sydney (AU)
- The University of Sydney (AU)
- Centenary Institute (AU)
- Taronga Conservation Society Australia (AU)
- UNSW Sydney (AU)
- Institute of Infection and Immunity (CA)
Publication Details
- Journal
- Journal of Virology
- Published
- 2025-09-04
- DOI
- https://doi.org/10.1128/jvi.00435-25
- Primary Topic
- Phagocytosis and Immune Regulation
- Type
- article
- Field-Weighted Citation Impact
- 0.00