tetano
Editor, Senior Moderator
Front Immunol
. 2024 Mar 26:15:1370511.
doi: 10.3389/fimmu.2024.1370511. eCollection 2024. Human surfactant protein A inhibits SARS-CoV-2 infectivity and alleviates lung injury in a mouse infection model
Ikechukwu B Jacob[SUP] 1 2 [/SUP], Amanda Gemmiti[SUP] 3 [/SUP], Weichuan Xiong[SUP] 1 [/SUP], Erin Reynolds[SUP] 2 [/SUP], Brian Nicholas[SUP] 3 [/SUP], Saravanan Thangamani[SUP] 2 [/SUP], Hongpeng Jia[SUP] 4 [/SUP], Guirong Wang[SUP] 1 2 [/SUP]
Affiliations
Introduction: SARS coronavirus 2 (SARS-CoV-2) infects human angiotensin-converting enzyme 2 (hACE2)-expressing lung epithelial cells through its spike (S) protein. The S protein is highly glycosylated and could be a target for lectins. Surfactant protein A (SP-A) is a collagen-containing C-type lectin, expressed by mucosal epithelial cells and mediates its antiviral activities by binding to viral glycoproteins.
Objective: This study examined the mechanistic role of human SP-A in SARS-CoV-2 infectivity and lung injury in vitro and in vivo.
Results: Human SP-A can bind both SARS-CoV-2 S protein and hACE2 in a dose-dependent manner (p<0.01). Pre-incubation of SARS-CoV-2 (Delta) with human SP-A inhibited virus binding and entry and reduced viral load in human lung epithelial cells, evidenced by the dose-dependent decrease in viral RNA, nucleocapsid protein (NP), and titer (p<0.01). We observed significant weight loss, increased viral burden, and mortality rate, and more severe lung injury in SARS-CoV-2 infected hACE2/SP-A KO mice (SP-A deficient mice with hACE2 transgene) compared to infected hACE2/mSP-A (K18) and hACE2/hSP-A1 (6A[SUP]2[/SUP]) mice (with both hACE2 and human SP-A1 transgenes) 6 Days Post-infection (DPI). Furthermore, increased SP-A level was observed in the saliva of COVID-19 patients compared to healthy controls (p<0.05), but severe COVID-19 patients had relatively lower SP-A levels than moderate COVID-19 patients (p<0.05).
Discussion: Collectively, human SP-A attenuates SARS-CoV-2-induced acute lung injury (ALI) by directly binding to the S protein and hACE2, and inhibiting its infectivity; and SP-A level in the saliva of COVID-19 patients might serve as a biomarker for COVID-19 severity.
Keywords: COVID-19; SARS-CoV-2; acute lung injury; biomarker; innate immunity; spike protein; surfactant protein A.
. 2024 Mar 26:15:1370511.
doi: 10.3389/fimmu.2024.1370511. eCollection 2024. Human surfactant protein A inhibits SARS-CoV-2 infectivity and alleviates lung injury in a mouse infection model
Ikechukwu B Jacob[SUP] 1 2 [/SUP], Amanda Gemmiti[SUP] 3 [/SUP], Weichuan Xiong[SUP] 1 [/SUP], Erin Reynolds[SUP] 2 [/SUP], Brian Nicholas[SUP] 3 [/SUP], Saravanan Thangamani[SUP] 2 [/SUP], Hongpeng Jia[SUP] 4 [/SUP], Guirong Wang[SUP] 1 2 [/SUP]
Affiliations
- PMID: 38596675
- PMCID: PMC11002091
- DOI: 10.3389/fimmu.2024.1370511
Introduction: SARS coronavirus 2 (SARS-CoV-2) infects human angiotensin-converting enzyme 2 (hACE2)-expressing lung epithelial cells through its spike (S) protein. The S protein is highly glycosylated and could be a target for lectins. Surfactant protein A (SP-A) is a collagen-containing C-type lectin, expressed by mucosal epithelial cells and mediates its antiviral activities by binding to viral glycoproteins.
Objective: This study examined the mechanistic role of human SP-A in SARS-CoV-2 infectivity and lung injury in vitro and in vivo.
Results: Human SP-A can bind both SARS-CoV-2 S protein and hACE2 in a dose-dependent manner (p<0.01). Pre-incubation of SARS-CoV-2 (Delta) with human SP-A inhibited virus binding and entry and reduced viral load in human lung epithelial cells, evidenced by the dose-dependent decrease in viral RNA, nucleocapsid protein (NP), and titer (p<0.01). We observed significant weight loss, increased viral burden, and mortality rate, and more severe lung injury in SARS-CoV-2 infected hACE2/SP-A KO mice (SP-A deficient mice with hACE2 transgene) compared to infected hACE2/mSP-A (K18) and hACE2/hSP-A1 (6A[SUP]2[/SUP]) mice (with both hACE2 and human SP-A1 transgenes) 6 Days Post-infection (DPI). Furthermore, increased SP-A level was observed in the saliva of COVID-19 patients compared to healthy controls (p<0.05), but severe COVID-19 patients had relatively lower SP-A levels than moderate COVID-19 patients (p<0.05).
Discussion: Collectively, human SP-A attenuates SARS-CoV-2-induced acute lung injury (ALI) by directly binding to the S protein and hACE2, and inhibiting its infectivity; and SP-A level in the saliva of COVID-19 patients might serve as a biomarker for COVID-19 severity.
Keywords: COVID-19; SARS-CoV-2; acute lung injury; biomarker; innate immunity; spike protein; surfactant protein A.