{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T22:43:25Z","timestamp":1790462605377,"version":"4.1.0"},"reference-count":40,"publisher":"Public Library of Science (PLoS)","issue":"10","license":[{"start":{"date-parts":[[2022,10,19]],"date-time":"2022-10-19T00:00:00Z","timestamp":1666137600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100005217","name":"National Center for Injury Prevention and Control","doi-asserted-by":"publisher","award":["U01 CE003384-01"],"award-info":[{"award-number":["U01 CE003384-01"]}],"id":[{"id":"10.13039\/100005217","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100011353","name":"Center for Clinical and Translational Science, University of Massachusetts","doi-asserted-by":"publisher","award":["U54 GM104940"],"award-info":[{"award-number":["U54 GM104940"]}],"id":[{"id":"10.13039\/100011353","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007875","name":"Tulane University","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007875","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000056","name":"National Institute of Nursing Research","doi-asserted-by":"publisher","award":["R35 HL139930"],"award-info":[{"award-number":["R35 HL139930"]}],"id":[{"id":"10.13039\/100000056","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000968","name":"American Heart Association","doi-asserted-by":"publisher","award":["19CDA34660287"],"award-info":[{"award-number":["19CDA34660287"]}],"id":[{"id":"10.13039\/100000968","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p>The endothelial glycocalyx (EGX) contributes to the permeability barrier of vessels and regulates the coagulation cascade. EGX damage, which occurs in numerous disease states, including sepsis and trauma, results in endotheliopathy. While influenza and other viral infections are known to cause endothelial dysfunction, their effect on the EGX has not been described. We hypothesized that the H1N1 influenza virus would cause EGX degradation. Human umbilical vein endothelial cells (HUVECs) were exposed to varying multiplicities of infection (MOI) of the H1N1 strain of influenza virus for 24 hours. A dose-dependent effect was examined by using an MOI of 5 (n = 541), 15 (n = 714), 30 (n = 596), and 60 (n = 653) and compared to a control (n = 607). Cells were fixed and stained with FITC-labelled wheat germ agglutinin to quantify EGX. There was no difference in EGX intensity after exposure to H1N1 at an MOI of 5 compared to control (6.20 vs. 6.56 Arbitrary Units (AU), p = 0.50). EGX intensity was decreased at an MOI of 15 compared to control (5.36 vs. 6.56 AU, p&lt;0.001). The degree of EGX degradation was worse at higher doses of the H1N1 virus; however, the decrease in EGX intensity was maximized at an MOI of 30. Injury at MOI of 60 was not worse than MOI of 30. (4.17 vs. 4.47 AU, p = 0.13). The H1N1 virus induces endothelial dysfunction by causing EGX degradation in a dose-dependent fashion. Further studies are needed to characterize the role of this EGX damage in causing clinically significant lung injury during acute viral infection.<\/jats:p>","DOI":"10.1371\/journal.pone.0276232","type":"journal-article","created":{"date-parts":[[2022,10,19]],"date-time":"2022-10-19T17:36:18Z","timestamp":1666200978000},"page":"e0276232","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":14,"title":["Glycocalyx degradation and the endotheliopathy of viral infection"],"prefix":"10.1371","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6289-2129","authenticated-orcid":true,"given":"Sharven","family":"Taghavi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah","family":"Abdullah","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Farhana","family":"Shaheen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6459-9839","authenticated-orcid":true,"given":"Lauren","family":"Mueller","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brennan","family":"Gagen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan","family":"Duchesne","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chad","family":"Steele","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Derek","family":"Pociask","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jay","family":"Kolls","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olan","family":"Jackson-Weaver","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2022,10,19]]},"reference":[{"issue":"1","key":"pone.0276232.ref001","doi-asserted-by":"crossref","first-page":"e23494","DOI":"10.4161\/tisb.23494","article-title":"The endothelial glycocalyx","volume":"1","author":"Y Yang","year":"2013","journal-title":"Tissue Barriers"},{"issue":"102","key":"pone.0276232.ref002","article-title":"Neferine Protects Endothelial Glycocalyx via Mitochondrial ROS in Lipopolysaccharide-Induced Acute Respiratory Distress Syndrome","volume":"9","author":"X-Y Liu","year":"2018","journal-title":"Frontiers in Physiology"},{"issue":"5","key":"pone.0276232.ref003","doi-asserted-by":"crossref","first-page":"1070","DOI":"10.1097\/TA.0000000000002427","article-title":"Hypoxia\/reoxygenation decreases endothelial glycocalyx via reactive oxygen species and calcium signaling in a cellular model for shock","volume":"87","author":"O Jackson-Weaver","year":"2019","journal-title":"J Trauma Acute Care Surg"},{"issue":"3","key":"pone.0276232.ref004","doi-asserted-by":"crossref","first-page":"611","DOI":"10.4269\/ajtmh.14-0232","article-title":"Endothelial glycocalyx damage is associated with leptospirosis acute kidney injury","volume":"92","author":"AB Lib\u00f3rio","year":"2015","journal-title":"Am J Trop Med Hyg"},{"issue":"9","key":"pone.0276232.ref005","doi-asserted-by":"crossref","first-page":"2742","DOI":"10.2337\/db15-1662","article-title":"Hyaluronidase 1 Deficiency Preserves Endothelial Function and Glycocalyx Integrity in Early Streptozotocin-Induced Diabetes","volume":"65","author":"S Dogn\u00e9","year":"2016","journal-title":"Diabetes"},{"issue":"1","key":"pone.0276232.ref006","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1097\/TA.0000000000001695","article-title":"Poor microcirculatory flow dynamics are associated with endothelial cell damage and glycocalyx shedding after traumatic hemorrhagic shock","volume":"84","author":"DN Naumann","year":"2018","journal-title":"J Trauma Acute Care Surg"},{"issue":"10","key":"pone.0276232.ref007","doi-asserted-by":"crossref","first-page":"e0254985","DOI":"10.1371\/journal.pone.0254985","article-title":"Interleukin-22 mitigates acute respiratory distress syndrome (ARDS)","volume":"16","author":"S Taghavi","year":"2021","journal-title":"PLoS One"},{"issue":"5","key":"pone.0276232.ref008","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1016\/j.bj.2020.08.007","article-title":"Endothelial glycocalyx damage as a systemic inflammatory microvascular endotheliopathy in COVID-19","volume":"43","author":"M. Yamaoka-Tojo","year":"2020","journal-title":"biomedical journal"},{"issue":"7","key":"pone.0276232.ref009","doi-asserted-by":"crossref","first-page":"0300060520939746","DOI":"10.1177\/0300060520939746","article-title":"Endothelial activation and dysfunction in metabolic syndrome, type 2 diabetes and coronavirus disease 2019","volume":"48","author":"MR Hayden","year":"2020","journal-title":"Journal of International Medical Research"},{"key":"pone.0276232.ref010","doi-asserted-by":"crossref","first-page":"111694","DOI":"10.1016\/j.fct.2020.111694","article-title":"Tocilizumab improves oxidative stress and endothelial glycocalyx: A mechanism that may explain the effects of biological treatment on COVID-19","volume":"145","author":"I Ikonomidis","year":"2020","journal-title":"Food and Chemical Toxicology"},{"issue":"1","key":"pone.0276232.ref011","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41598-021-91231-1","article-title":"Endothelial glycocalyx shields the interaction of SARS-CoV-2 spike protein with ACE2 receptors","volume":"11","author":"M Targosz-Korecka","year":"2021","journal-title":"Scientific reports"},{"issue":"1","key":"pone.0276232.ref012","doi-asserted-by":"crossref","DOI":"10.1186\/s40560-021-00543-x","article-title":"A longitudinal change of syndecan-1 predicts risk of acute respiratory distress syndrome and cumulative fluid balance in patients with septic shock: a preliminary study","volume":"9","author":"Y Kajita","year":"2021","journal-title":"Journal of Intensive Care"},{"key":"pone.0276232.ref013","first-page":"8(1)","article-title":"Endothelial glycocalyx shedding in the acute respiratory distress syndrome after flu syndrome","author":"MN Benatti","year":"2020","journal-title":"Journal of Intensive Care"},{"issue":"5","key":"pone.0276232.ref014","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1016\/j.bj.2020.08.007","article-title":"Endothelial glycocalyx damage as a systemic inflammatory microvascular endotheliopathy in COVID-19","volume":"43","author":"M. Yamaoka-Tojo","year":"2020","journal-title":"Biomed J"},{"issue":"2","key":"pone.0276232.ref015","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1128\/mr.44.2.303-330.1980","article-title":"Pathogenicity of influenza virus","volume":"44","author":"C Sweet","year":"1980","journal-title":"Microbiol Rev"},{"issue":"Pt 11","key":"pone.0276232.ref016","doi-asserted-by":"crossref","first-page":"2821","DOI":"10.1099\/0022-1317-78-11-2821","article-title":"Differential induction of cytotoxicity and apoptosis by influenza virus strains of differing virulence","volume":"78","author":"GE Price","year":"1997","journal-title":"J Gen Virol"},{"issue":"1","key":"pone.0276232.ref017","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1186\/s40560-020-00488-7","article-title":"Endothelial glycocalyx shedding in the acute respiratory distress syndrome after flu syndrome","volume":"8","author":"MN Benatti","year":"2020","journal-title":"J Intensive Care"},{"issue":"1","key":"pone.0276232.ref018","first-page":"1","article-title":"Association between plasma glycocalyx component levels and poor prognosis in severe influenza type A (H1N1)","volume":"12","author":"X Huang","year":"2022","journal-title":"Scientific reports"},{"issue":"3","key":"pone.0276232.ref019","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1007\/s00011-019-01314-z","article-title":"Crocin alleviates lipopolysaccharide-induced acute respiratory distress syndrome by protecting against glycocalyx damage and suppressing inflammatory signaling pathways","volume":"69","author":"D Zhang","year":"2020","journal-title":"Inflamm Res"},{"key":"pone.0276232.ref020","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1016\/j.intimp.2018.10.001","article-title":"Berberine alleviates endothelial glycocalyx degradation and promotes glycocalyx restoration in LPS-induced ARDS","volume":"65","author":"L Huang","year":"2018","journal-title":"Int Immunopharmacol"},{"issue":"2","key":"pone.0276232.ref021","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1097\/TA.0000000000003019","article-title":"Interleukin 22 mitigates endothelial glycocalyx shedding after lipopolysaccharide injury","volume":"90","author":"S Taghavi","year":"2021","journal-title":"J Trauma Acute Care Surg"},{"issue":"8","key":"pone.0276232.ref022","doi-asserted-by":"crossref","first-page":"1908","DOI":"10.1161\/ATVBAHA.111.225268","article-title":"Imaging the endothelial glycocalyx in vitro by rapid freezing\/freeze substitution transmission electron microscopy","volume":"31","author":"EE Ebong","year":"2011","journal-title":"Arterioscler Thromb Vasc Biol"},{"issue":"6","key":"pone.0276232.ref023","doi-asserted-by":"crossref","first-page":"1166","DOI":"10.1016\/j.amjsurg.2017.09.018","article-title":"Disparate effects of catecholamines under stress conditions on endothelial glycocalyx injury: An in vitro model","volume":"214","author":"JV Martin","year":"2017","journal-title":"Am J Surg"},{"issue":"4","key":"pone.0276232.ref024","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1006\/meth.2001.1262","article-title":"Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method","volume":"25","author":"KJ Livak","year":"2001","journal-title":"Methods"},{"issue":"1","key":"pone.0276232.ref025","doi-asserted-by":"crossref","first-page":"e22052","DOI":"10.1096\/fj.202101100RR","article-title":"Pathogenesis of COVID\u201019 described through the lens of an undersulfated and degraded epithelial and endothelial glycocalyx","volume":"36","author":"HN du Preez","year":"2022","journal-title":"The FASEB Journal"},{"issue":"8","key":"pone.0276232.ref026","doi-asserted-by":"crossref","first-page":"1217","DOI":"10.1038\/nm.2843","article-title":"The pulmonary endothelial glycocalyx regulates neutrophil adhesion and lung injury during experimental sepsis","volume":"18","author":"EP Schmidt","year":"2012","journal-title":"Nat Med"},{"key":"pone.0276232.ref027","first-page":"2016","article-title":"Influenza A Virus and Influenza B Virus Can Induce Apoptosis via Intrinsic or Extrinsic Pathways and Also via NF-kappa B in a Time and Dose Dependent Manner","author":"I El-Sayed","year":"2016","journal-title":"Biochemistry Research International"},{"issue":"3","key":"pone.0276232.ref028","doi-asserted-by":"crossref","first-page":"H647","DOI":"10.1152\/ajpheart.00090.2018","article-title":"Role of matrix metalloproteinases and histone deacetylase in oxidative stress-induced degradation of the endothelial glycocalyx","volume":"316","author":"MM Ali","year":"2019","journal-title":"Am J Physiol Heart Circ Physiol"},{"issue":"3","key":"pone.0276232.ref029","doi-asserted-by":"crossref","first-page":"e32418","DOI":"10.1371\/journal.pone.0032418","article-title":"A metalloproteinase secreted by Streptococcus pneumoniae removes membrane mucin MUC16 from the epithelial glycocalyx barrier","volume":"7","author":"B Govindarajan","year":"2012","journal-title":"PLoS One"},{"key":"pone.0276232.ref030","doi-asserted-by":"crossref","first-page":"912726","DOI":"10.1155\/2015\/912726","article-title":"Dexamethasone Suppressed LPS-Induced Matrix Metalloproteinase and Its Effect on Endothelial Glycocalyx Shedding","volume":"2015","author":"N Cui","year":"2015","journal-title":"Mediators Inflamm"},{"key":"pone.0276232.ref031","first-page":"1694","volume-title":"ADAM-15 and glycocalyx shedding: a new perspective on sepsis-related vasomotor dysfunction","author":"JD Horowitz","year":"2018"},{"issue":"4","key":"pone.0276232.ref032","doi-asserted-by":"crossref","first-page":"e1007033","DOI":"10.1371\/journal.ppat.1007033","article-title":"Macrophage migration inhibitory factor is critical for dengue NS1-induced endothelial glycocalyx degradation and hyperpermeability","volume":"14","author":"H-R Chen","year":"2018","journal-title":"PLoS pathogens"},{"key":"pone.0276232.ref033","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1016\/j.cimid.2017.11.002","article-title":"Clarithromycin suppresses induction of monocyte chemoattractant protein-1 and matrix metalloproteinase-9 and improves pathological changes in the lungs and heart of mice infected with influenza A virus","volume":"56","author":"E Takahashi","year":"2018","journal-title":"Comp Immunol Microbiol Infect Dis"},{"issue":"1","key":"pone.0276232.ref034","doi-asserted-by":"crossref","first-page":"228","DOI":"10.1016\/j.bbrc.2007.01.137","article-title":"The role of endothelial glycocalyx components in mechanotransduction of fluid shear stress","volume":"355","author":"MY Pahakis","year":"2007","journal-title":"Biochem Biophys Res Commun"},{"issue":"11","key":"pone.0276232.ref035","doi-asserted-by":"crossref","first-page":"2885","DOI":"10.1681\/ASN.2007010119","article-title":"Glomerular endothelial glycocalyx constitutes a barrier to protein permeability","volume":"18","author":"A Singh","year":"2007","journal-title":"J Am Soc Nephrol"},{"issue":"74","key":"pone.0276232.ref036","doi-asserted-by":"crossref","first-page":"2290","DOI":"10.1098\/rsif.2011.0901","article-title":"Spatio-temporal development of the endothelial glycocalyx layer and its mechanical property in vitro","volume":"9","author":"K Bai","year":"2012","journal-title":"J R Soc Interface"},{"key":"pone.0276232.ref037","doi-asserted-by":"crossref","first-page":"119376","DOI":"10.1016\/j.lfs.2021.119376","article-title":"Heparin prevents in vitro glycocalyx shedding induced by plasma from COVID-19 patients","volume":"276","author":"SR Potje","year":"2021","journal-title":"Life sciences"},{"key":"pone.0276232.ref038","doi-asserted-by":"crossref","first-page":"172413","DOI":"10.1016\/j.ejphar.2019.172413","article-title":"Berberine inhibits low shear stress-induced glycocalyx degradation via modulating AMPK and p47(phox)\/Hyal2 signal pathway","volume":"856","author":"H Yang","year":"2019","journal-title":"Eur J Pharmacol"},{"issue":"2","key":"pone.0276232.ref039","doi-asserted-by":"crossref","first-page":"C137","DOI":"10.1152\/ajpcell.00187.2012","article-title":"Hemodynamic shear stress characteristic of atherosclerosis-resistant regions promotes glycocalyx formation in cultured endothelial cells","volume":"304","author":"A Koo","year":"2013","journal-title":"Am J Physiol Cell Physiol"},{"issue":"6","key":"pone.0276232.ref040","doi-asserted-by":"crossref","first-page":"e21643","DOI":"10.1096\/fj.201802376RRRR","article-title":"An improved in vitro model for studying the structural and functional properties of the endothelial glycocalyx in arteries, capillaries and veins","volume":"35","author":"EM Siren","year":"2021","journal-title":"The FASEB Journal"}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0276232","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,10,6]],"date-time":"2024-10-06T03:50:08Z","timestamp":1728186608000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0276232"}},"subtitle":[],"editor":[{"given":"M\u00e1ria A.","family":"Deli","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2022,10,19]]},"references-count":40,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2022,10,19]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0276232","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,10,19]]}}}