tetano
Editor, Senior Moderator
J Mol Cell Biol
. 2023 May 1;mjad030.
doi: 10.1093/jmcb/mjad030. Online ahead of print. Human galectin-9 potently enhances SARS-CoV-2 replication and inflammation in airway epithelial cells
Li Du[SUP] 1 2 [/SUP], Mohamed S Bouzidi[SUP] 1 2 [/SUP], Akshay Gala[SUP] 1 2 [/SUP], Fred Deiter[SUP] 3 4 [/SUP], Jean-Noël Billaud[SUP] 5 [/SUP], Stephen T Yeung[SUP] 6 [/SUP], Prerna Dabral[SUP] 1 2 [/SUP], Jing Jin[SUP] 1 2 [/SUP], Graham Simmons[SUP] 1 2 [/SUP], Zain Y Dossani[SUP] 1 2 [/SUP], Toshiro Niki[SUP] 7 [/SUP], Lishomwa C Ndhlovu[SUP] 6 [/SUP], John R Greenland[SUP] 3 4 [/SUP], Satish K Pillai[SUP] 1 2 [/SUP]
Affiliations
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has caused a global economic and health crisis. Recently, plasma levels of galectin-9 (Gal-9), a β-galactoside-binding lectin involved in immune regulation and viral immunopathogenesis, were reported to be elevated in the setting of severe COVID-19 disease. However, the impact of Gal-9 on SARS-CoV-2 infection and immunopathology remained to be elucidated. In this study, we demonstrate that Gal-9 treatment potently enhances SARS-CoV-2 replication in human airway epithelial cells (AECs), including immortalized AECs and primary AECs cultured at the air-liquid interface. Gal-9-glycan interactions promote SARS-CoV-2 attachment and entry into AECs in an angiotensin-converting enzyme 2 (ACE2)-dependent manner, enhancing the binding of the viral spike protein to ACE2. Transcriptomic analysis revealed that Gal-9 and SARS-CoV-2 infection synergistically induced the expression of key pro-inflammatory programs in AECs including the IL-6, IL-8, IL-17, EIF2, and TNFα signaling pathways. Our findings suggest that manipulation of Gal-9 should be explored as a therapeutic strategy for SARS-CoV-2 infection.
Keywords: SARS-CoV-2; airway epithelial cells; galectin-9; inflammation.
. 2023 May 1;mjad030.
doi: 10.1093/jmcb/mjad030. Online ahead of print. Human galectin-9 potently enhances SARS-CoV-2 replication and inflammation in airway epithelial cells
Li Du[SUP] 1 2 [/SUP], Mohamed S Bouzidi[SUP] 1 2 [/SUP], Akshay Gala[SUP] 1 2 [/SUP], Fred Deiter[SUP] 3 4 [/SUP], Jean-Noël Billaud[SUP] 5 [/SUP], Stephen T Yeung[SUP] 6 [/SUP], Prerna Dabral[SUP] 1 2 [/SUP], Jing Jin[SUP] 1 2 [/SUP], Graham Simmons[SUP] 1 2 [/SUP], Zain Y Dossani[SUP] 1 2 [/SUP], Toshiro Niki[SUP] 7 [/SUP], Lishomwa C Ndhlovu[SUP] 6 [/SUP], John R Greenland[SUP] 3 4 [/SUP], Satish K Pillai[SUP] 1 2 [/SUP]
Affiliations
- PMID: 37127426
- DOI: 10.1093/jmcb/mjad030
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has caused a global economic and health crisis. Recently, plasma levels of galectin-9 (Gal-9), a β-galactoside-binding lectin involved in immune regulation and viral immunopathogenesis, were reported to be elevated in the setting of severe COVID-19 disease. However, the impact of Gal-9 on SARS-CoV-2 infection and immunopathology remained to be elucidated. In this study, we demonstrate that Gal-9 treatment potently enhances SARS-CoV-2 replication in human airway epithelial cells (AECs), including immortalized AECs and primary AECs cultured at the air-liquid interface. Gal-9-glycan interactions promote SARS-CoV-2 attachment and entry into AECs in an angiotensin-converting enzyme 2 (ACE2)-dependent manner, enhancing the binding of the viral spike protein to ACE2. Transcriptomic analysis revealed that Gal-9 and SARS-CoV-2 infection synergistically induced the expression of key pro-inflammatory programs in AECs including the IL-6, IL-8, IL-17, EIF2, and TNFα signaling pathways. Our findings suggest that manipulation of Gal-9 should be explored as a therapeutic strategy for SARS-CoV-2 infection.
Keywords: SARS-CoV-2; airway epithelial cells; galectin-9; inflammation.