tetano
Editor, Senior Moderator
Proc Natl Acad Sci U S A
. 2025 Oct 28;122(43):e2521209122.
doi: 10.1073/pnas.2521209122. Epub 2025 Oct 24. Glycan recognition by collectin-11 drives SARS-CoV-2 infectivity and membrane injury of respiratory epithelial cells
Anastasia Polycarpou[SUP] #[/SUP][SUP] 1 [/SUP], Tara Wagner-Gamble[SUP] #[/SUP][SUP] 2 [/SUP], Roseanna Greenlaw[SUP] #[/SUP][SUP] 1 [/SUP], Lauren O'Neill[SUP] #[/SUP][SUP] 2 [/SUP], Varsha Kanabar[SUP] 2 [/SUP], Alanoud Alrehaili[SUP] 3 [/SUP], Yusun Jeon[SUP] 1 [/SUP], Jonathan Baker[SUP] 4 [/SUP], Mona Bafadhel[SUP] 4 [/SUP], Hataf Khan[SUP] 2 [/SUP], Michael H Malim[SUP] 2 [/SUP], Marco Romano[SUP] 1 [/SUP], Conrad A Farrar[SUP] 1 [/SUP], Dorota Smolarek[SUP] 1 [/SUP], Rocio Martinez-Nunez[SUP] 2 [/SUP], Katie J Doores[SUP] 2 [/SUP], Russell Wallis[SUP] 3 [/SUP], Linda S Klavinskis[SUP] #[/SUP][SUP] 2 [/SUP], Steven H Sacks[SUP] #[/SUP][SUP] 1 [/SUP]
Affiliations
SARS-CoV-2 respiratory-tract infection affects both vaccinated and unvaccinated persons suggesting factors besides adaptive immunity are operative. We investigated the role of collectin-11 (CL-11), an epithelial-secreted carbohydrate-binding lectin that drives innate immunity and eliminates pathogens by complement activation. SARS-CoV-2, despite binding CL-11 to activate complement, was resistant to lysis. Remarkably, opsonization by CL-11 enhanced virus production by infected respiratory epithelial cells independently of complement. Furthermore, infected cells expressing SARS-CoV-2 spike protein displayed enhanced vulnerability to CL-11 binding and membrane attack by complement. The mechanism of enhanced infectivity was ablated in the presence of L-fucose, which occupied the extended carbohydrate-binding cleft of CL-11 in a crystallographic analysis of complexes between L-fucose and CL-11. Our study suggests pathogenicity of SARS-CoV-2 is related to complement-resistance together with enhanced infectivity and injury of respiratory epithelial cells mediated by locally released CL-11.
Keywords: SARS-CoV-2; collectin-11; complement proteins; glycans.
. 2025 Oct 28;122(43):e2521209122.
doi: 10.1073/pnas.2521209122. Epub 2025 Oct 24. Glycan recognition by collectin-11 drives SARS-CoV-2 infectivity and membrane injury of respiratory epithelial cells
Anastasia Polycarpou[SUP] #[/SUP][SUP] 1 [/SUP], Tara Wagner-Gamble[SUP] #[/SUP][SUP] 2 [/SUP], Roseanna Greenlaw[SUP] #[/SUP][SUP] 1 [/SUP], Lauren O'Neill[SUP] #[/SUP][SUP] 2 [/SUP], Varsha Kanabar[SUP] 2 [/SUP], Alanoud Alrehaili[SUP] 3 [/SUP], Yusun Jeon[SUP] 1 [/SUP], Jonathan Baker[SUP] 4 [/SUP], Mona Bafadhel[SUP] 4 [/SUP], Hataf Khan[SUP] 2 [/SUP], Michael H Malim[SUP] 2 [/SUP], Marco Romano[SUP] 1 [/SUP], Conrad A Farrar[SUP] 1 [/SUP], Dorota Smolarek[SUP] 1 [/SUP], Rocio Martinez-Nunez[SUP] 2 [/SUP], Katie J Doores[SUP] 2 [/SUP], Russell Wallis[SUP] 3 [/SUP], Linda S Klavinskis[SUP] #[/SUP][SUP] 2 [/SUP], Steven H Sacks[SUP] #[/SUP][SUP] 1 [/SUP]
Affiliations
- PMID: 41134631
- DOI: 10.1073/pnas.2521209122
SARS-CoV-2 respiratory-tract infection affects both vaccinated and unvaccinated persons suggesting factors besides adaptive immunity are operative. We investigated the role of collectin-11 (CL-11), an epithelial-secreted carbohydrate-binding lectin that drives innate immunity and eliminates pathogens by complement activation. SARS-CoV-2, despite binding CL-11 to activate complement, was resistant to lysis. Remarkably, opsonization by CL-11 enhanced virus production by infected respiratory epithelial cells independently of complement. Furthermore, infected cells expressing SARS-CoV-2 spike protein displayed enhanced vulnerability to CL-11 binding and membrane attack by complement. The mechanism of enhanced infectivity was ablated in the presence of L-fucose, which occupied the extended carbohydrate-binding cleft of CL-11 in a crystallographic analysis of complexes between L-fucose and CL-11. Our study suggests pathogenicity of SARS-CoV-2 is related to complement-resistance together with enhanced infectivity and injury of respiratory epithelial cells mediated by locally released CL-11.
Keywords: SARS-CoV-2; collectin-11; complement proteins; glycans.