Author: Simons, Peter; Rinaldi, Derek A.; Bondu, Virginie; Kell, Alison M.; Bradfute, Steven; Lidke, Diane S.; Buranda, Tione
Title: Integrin activation is an essential component of SARS-CoV-2 infection Cord-id: ej8lu2io Document date: 2021_10_14
ID: ej8lu2io
Snippet: SARS-CoV-2 infection depends on binding its spike (S) protein to angiotensin-converting enzyme 2 (ACE2). The S protein expresses an RGD motif, suggesting that integrins may be co-receptors. Here, we UV-inactivated SARS-CoV-2 and fluorescently labeled the envelope membrane with octadecyl rhodamine B (R18) to explore the role of integrin activation in mediating cell entry and productive infection. We used flow cytometry and confocal microscopy to show that SARS-CoV-2(R18) particles engage basal-st
Document: SARS-CoV-2 infection depends on binding its spike (S) protein to angiotensin-converting enzyme 2 (ACE2). The S protein expresses an RGD motif, suggesting that integrins may be co-receptors. Here, we UV-inactivated SARS-CoV-2 and fluorescently labeled the envelope membrane with octadecyl rhodamine B (R18) to explore the role of integrin activation in mediating cell entry and productive infection. We used flow cytometry and confocal microscopy to show that SARS-CoV-2(R18) particles engage basal-state integrins. Furthermore, we demonstrate that Mn(2+), which induces integrin extension, enhances cell entry of SARS-CoV-2(R18). We also show that one class of integrin antagonist, which binds to the αI MIDAS site and stabilizes the inactive, closed conformation, selectively inhibits the engagement of SARS-CoV-2(R18) with basal state integrins, but is ineffective against Mn(2+)-activated integrins. RGD-integrin antagonists inhibited SARS-CoV-2(R18) binding regardless of integrin activation status. Integrins transmit signals bidirectionally: 'inside-out' signaling primes the ligand-binding function of integrins via a talin-dependent mechanism, and 'outside-in' signaling occurs downstream of integrin binding to macromolecular ligands. Outside-in signaling is mediated by Gα(13). Using cell-permeable peptide inhibitors of talin and Gα(13) binding to the cytoplasmic tail of an integrin's β subunit, we demonstrate that talin-mediated signaling is essential for productive infection.
Search related documents:
Co phrase search for related documents- Try single phrases listed below for: 1
Co phrase search for related documents, hyperlinks ordered by date