Human surfactant protein A inhibits SARS-CoV-2 infectivity and alleviates lung injury in a mouse infection model
IntroductionSARS 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...
Main Authors: | , , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
Frontiers Media S.A.
2024-03-01
|
Series: | Frontiers in Immunology |
Subjects: | |
Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2024.1370511/full |
_version_ | 1797244982219767808 |
---|---|
author | Ikechukwu B. Jacob Ikechukwu B. Jacob Amanda Gemmiti Weichuan Xiong Erin Reynolds Brian Nicholas Saravanan Thangamani Hongpeng Jia Guirong Wang Guirong Wang |
author_facet | Ikechukwu B. Jacob Ikechukwu B. Jacob Amanda Gemmiti Weichuan Xiong Erin Reynolds Brian Nicholas Saravanan Thangamani Hongpeng Jia Guirong Wang Guirong Wang |
author_sort | Ikechukwu B. Jacob |
collection | DOAJ |
description | IntroductionSARS 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.ObjectiveThis study examined the mechanistic role of human SP-A in SARS-CoV-2 infectivity and lung injury in vitro and in vivo.ResultsHuman 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 (6A2) 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).DiscussionCollectively, 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. |
first_indexed | 2024-04-24T19:19:39Z |
format | Article |
id | doaj.art-64a2bb928cd844d0ac49d07dda507a5c |
institution | Directory Open Access Journal |
issn | 1664-3224 |
language | English |
last_indexed | 2024-04-24T19:19:39Z |
publishDate | 2024-03-01 |
publisher | Frontiers Media S.A. |
record_format | Article |
series | Frontiers in Immunology |
spelling | doaj.art-64a2bb928cd844d0ac49d07dda507a5c2024-03-26T04:19:47ZengFrontiers Media S.A.Frontiers in Immunology1664-32242024-03-011510.3389/fimmu.2024.13705111370511Human surfactant protein A inhibits SARS-CoV-2 infectivity and alleviates lung injury in a mouse infection modelIkechukwu B. Jacob0Ikechukwu B. Jacob1Amanda Gemmiti2Weichuan Xiong3Erin Reynolds4Brian Nicholas5Saravanan Thangamani6Hongpeng Jia7Guirong Wang8Guirong Wang9Department of Surgery, the State University of New York (SUNY) Upstate Medical University, Syracuse, NY, United StatesDepartment of Microbiology & Immunology, SUNY Upstate Medical University, Syracuse, NY, United StatesDepartment of Otolaryngology, SUNY Upstate Medical University, Syracuse, NY, United StatesDepartment of Surgery, the State University of New York (SUNY) Upstate Medical University, Syracuse, NY, United StatesDepartment of Microbiology & Immunology, SUNY Upstate Medical University, Syracuse, NY, United StatesDepartment of Otolaryngology, SUNY Upstate Medical University, Syracuse, NY, United StatesDepartment of Microbiology & Immunology, SUNY Upstate Medical University, Syracuse, NY, United StatesDepartment of Surgery, Johns-Hopkins University, Baltimore, MD, United StatesDepartment of Surgery, the State University of New York (SUNY) Upstate Medical University, Syracuse, NY, United StatesDepartment of Microbiology & Immunology, SUNY Upstate Medical University, Syracuse, NY, United StatesIntroductionSARS 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.ObjectiveThis study examined the mechanistic role of human SP-A in SARS-CoV-2 infectivity and lung injury in vitro and in vivo.ResultsHuman 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 (6A2) 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).DiscussionCollectively, 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.https://www.frontiersin.org/articles/10.3389/fimmu.2024.1370511/fullacute lung injurybiomarkerCOVID-19innate immunitySARS-CoV-2spike protein |
spellingShingle | Ikechukwu B. Jacob Ikechukwu B. Jacob Amanda Gemmiti Weichuan Xiong Erin Reynolds Brian Nicholas Saravanan Thangamani Hongpeng Jia Guirong Wang Guirong Wang Human surfactant protein A inhibits SARS-CoV-2 infectivity and alleviates lung injury in a mouse infection model Frontiers in Immunology acute lung injury biomarker COVID-19 innate immunity SARS-CoV-2 spike protein |
title | Human surfactant protein A inhibits SARS-CoV-2 infectivity and alleviates lung injury in a mouse infection model |
title_full | Human surfactant protein A inhibits SARS-CoV-2 infectivity and alleviates lung injury in a mouse infection model |
title_fullStr | Human surfactant protein A inhibits SARS-CoV-2 infectivity and alleviates lung injury in a mouse infection model |
title_full_unstemmed | Human surfactant protein A inhibits SARS-CoV-2 infectivity and alleviates lung injury in a mouse infection model |
title_short | Human surfactant protein A inhibits SARS-CoV-2 infectivity and alleviates lung injury in a mouse infection model |
title_sort | human surfactant protein a inhibits sars cov 2 infectivity and alleviates lung injury in a mouse infection model |
topic | acute lung injury biomarker COVID-19 innate immunity SARS-CoV-2 spike protein |
url | https://www.frontiersin.org/articles/10.3389/fimmu.2024.1370511/full |
work_keys_str_mv | AT ikechukwubjacob humansurfactantproteinainhibitssarscov2infectivityandalleviateslunginjuryinamouseinfectionmodel AT ikechukwubjacob humansurfactantproteinainhibitssarscov2infectivityandalleviateslunginjuryinamouseinfectionmodel AT amandagemmiti humansurfactantproteinainhibitssarscov2infectivityandalleviateslunginjuryinamouseinfectionmodel AT weichuanxiong humansurfactantproteinainhibitssarscov2infectivityandalleviateslunginjuryinamouseinfectionmodel AT erinreynolds humansurfactantproteinainhibitssarscov2infectivityandalleviateslunginjuryinamouseinfectionmodel AT briannicholas humansurfactantproteinainhibitssarscov2infectivityandalleviateslunginjuryinamouseinfectionmodel AT saravananthangamani humansurfactantproteinainhibitssarscov2infectivityandalleviateslunginjuryinamouseinfectionmodel AT hongpengjia humansurfactantproteinainhibitssarscov2infectivityandalleviateslunginjuryinamouseinfectionmodel AT guirongwang humansurfactantproteinainhibitssarscov2infectivityandalleviateslunginjuryinamouseinfectionmodel AT guirongwang humansurfactantproteinainhibitssarscov2infectivityandalleviateslunginjuryinamouseinfectionmodel |