tetano
Editor, Senior Moderator
J Biol Chem
. 2022 Feb 9;101710.
doi: 10.1016/j.jbc.2022.101710. Online ahead of print.
Integrin mediates cell entry of the SARS-CoV-2 virus independent of cellular receptor ACE2
Jiamnin Liu[SUP] 1 [/SUP], Fan Lu[SUP] 2 [/SUP], Yinghua Chen[SUP] 3 [/SUP], Edward Plow[SUP] 1 [/SUP], Jun Qin[SUP] 4 [/SUP]
Affiliations
Abstract
Coronavirus disease 2019 (COVID-19) is a highly contagious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). It is broadly accepted that SARS-CoV-2 utilizes its spike protein to recognize the extracellular domain of angiotensin-converting enzyme 2 (ACE2) to enter cells for viral infection. However, other mechanisms of SARS-CoV-2 cell entry may occur. We show quantitatively that the SARS-CoV-2 spike protein also binds to the extracellular domain of broadly expressed integrin α5β1 with an affinity comparable to that of SARS-CoV-2 binding to ACE2. More importantly, we provide direct evidence that such binding promotes the internalization of SARS-CoV-2 into non-ACE2 cells in a manner critically dependent upon the activation of the integrin. Our data demonstrate an alternative pathway for the cell entry of SARS-CoV-2, suggesting that upon initial ACE2-mediated invasion of the virus in the respiratory system, which is known to trigger an immune response and secretion of cytokines to activate integrin, the integrin-mediated cell invasion of SARS-CoV-2 into the respiratory system and other organs becomes effective, thereby promoting further infection and progression of COVID-19.
Keywords: COVID-19; Integrin; SARS-CoV-2; Virus infection.
. 2022 Feb 9;101710.
doi: 10.1016/j.jbc.2022.101710. Online ahead of print.
Integrin mediates cell entry of the SARS-CoV-2 virus independent of cellular receptor ACE2
Jiamnin Liu[SUP] 1 [/SUP], Fan Lu[SUP] 2 [/SUP], Yinghua Chen[SUP] 3 [/SUP], Edward Plow[SUP] 1 [/SUP], Jun Qin[SUP] 4 [/SUP]
Affiliations
- PMID: 35150743
- DOI: 10.1016/j.jbc.2022.101710
Abstract
Coronavirus disease 2019 (COVID-19) is a highly contagious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). It is broadly accepted that SARS-CoV-2 utilizes its spike protein to recognize the extracellular domain of angiotensin-converting enzyme 2 (ACE2) to enter cells for viral infection. However, other mechanisms of SARS-CoV-2 cell entry may occur. We show quantitatively that the SARS-CoV-2 spike protein also binds to the extracellular domain of broadly expressed integrin α5β1 with an affinity comparable to that of SARS-CoV-2 binding to ACE2. More importantly, we provide direct evidence that such binding promotes the internalization of SARS-CoV-2 into non-ACE2 cells in a manner critically dependent upon the activation of the integrin. Our data demonstrate an alternative pathway for the cell entry of SARS-CoV-2, suggesting that upon initial ACE2-mediated invasion of the virus in the respiratory system, which is known to trigger an immune response and secretion of cytokines to activate integrin, the integrin-mediated cell invasion of SARS-CoV-2 into the respiratory system and other organs becomes effective, thereby promoting further infection and progression of COVID-19.
Keywords: COVID-19; Integrin; SARS-CoV-2; Virus infection.