Dengue Virus NS1 Disrupts the Endothelial Glycocalyx, Leading to Hyperpermeability
Publication Date
July 14, 2016
Journal
PLOS Pathogens
Authors
Henry Puerta Guardo, Dustin R. Glasner & Eva Harris
Volume
12
Issue
7
Pages
e1005738
DOI
https://dx.plos.org/10.1371/journal.ppat.1005738
Publisher URL
http://journals.plos.org/plospathogens/article?id=10.1371%2Fjournal.ppat.1005738
Web of Science
000383366400024
Scopus
84980587131
Mendeley
http://www.mendeley.com/research/dengue-virus-ns1-disrupts-endothelial-glycocalyx-leading-hyperpermeability
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Mendeley | Further Information

{"title"=>"Dengue Virus NS1 Disrupts the Endothelial Glycocalyx, Leading to Hyperpermeability", "type"=>"journal", "authors"=>[{"first_name"=>"Henry", "last_name"=>"Puerta-Guardo", "scopus_author_id"=>"35409926100"}, {"first_name"=>"Dustin R.", "last_name"=>"Glasner", "scopus_author_id"=>"55595673300"}, {"first_name"=>"Eva", "last_name"=>"Harris", "scopus_author_id"=>"7403257174"}], "year"=>2016, "source"=>"PLoS Pathogens", "identifiers"=>{"doi"=>"10.1371/journal.ppat.1005738", "issn"=>"15537374", "sgr"=>"84982933441", "pui"=>"611582078", "scopus"=>"2-s2.0-84982933441", "pmid"=>"27416066"}, "id"=>"28ce9590-3ec8-390b-b3dc-87a3a2f16914", "abstract"=>"<title>Author Summary</title> <p>Dengue is the most prevalent mosquito-borne disease in humans and represents a major public health problem worldwide. Leakage of fluids and molecules from the bloodstream into tissues can lead to shock and potentially death and is a critical determinant of dengue disease severity. Recently, we showed that a secreted protein from dengue virus (DENV)-infected cells, non-structural protein 1 (NS1), can trigger increased leakage both in human cell culture and mouse models. It has been shown that NS1 can activate toll-like receptor 4 on peripheral blood mononuclear cells, leading to secretion of pro-inflammatory cytokines that can result in vascular leak. However, the mechanism by which NS1 triggers hyperpermeability directly in human endothelial cells remained undefined. The endothelial glycocalyx layer (EGL) is a network of membrane-bound molecules that lines endothelial cells on the inside of blood vessels, helping to regulate proper vascular function. Here, we show that DENV NS1 can disrupt the integrity of the EGL, inducing breakdown and shedding of key components. This is mediated by NS1 induction of cellular enzymes (e.g., sialidases, heparanase, and cathepsin L) that contribute to EGL alterations. Inhibitors that block these enzymes prevent both EGL disruption and endothelial permeability. These effects were all demonstrated to be specific to NS1 from DENV serotypes 1–4, as NS1 from the related West Nile Virus did not produce EGL alterations or increased leakage. Our study suggests a novel role for DENV NS1 in inducing EGL disruption to increase fluid leakage during severe dengue disease.</p>", "link"=>"http://www.mendeley.com/research/dengue-virus-ns1-disrupts-endothelial-glycocalyx-leading-hyperpermeability", "reader_count"=>68, "reader_count_by_academic_status"=>{"Unspecified"=>3, "Professor > Associate Professor"=>2, "Student > Doctoral Student"=>3, "Researcher"=>8, "Student > Ph. D. Student"=>21, "Student > Postgraduate"=>1, "Other"=>5, "Student > Master"=>13, "Student > Bachelor"=>12}, "reader_count_by_user_role"=>{"Unspecified"=>3, "Professor > Associate Professor"=>2, "Student > Doctoral Student"=>3, "Researcher"=>8, "Student > Ph. D. Student"=>21, "Student > Postgraduate"=>1, "Other"=>5, "Student > Master"=>13, "Student > Bachelor"=>12}, "reader_count_by_subject_area"=>{"Unspecified"=>4, "Biochemistry, Genetics and Molecular Biology"=>15, "Nursing and Health Professions"=>1, "Agricultural and Biological Sciences"=>17, "Medicine and Dentistry"=>9, "Veterinary Science and Veterinary Medicine"=>2, "Pharmacology, Toxicology and Pharmaceutical Science"=>1, "Chemistry"=>5, "Immunology and Microbiology"=>14}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>9}, "Chemistry"=>{"Chemistry"=>5}, "Immunology and Microbiology"=>{"Immunology and Microbiology"=>14}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>17}, "Nursing and Health Professions"=>{"Nursing and Health Professions"=>1}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>15}, "Unspecified"=>{"Unspecified"=>4}, "Pharmacology, Toxicology and Pharmaceutical Science"=>{"Pharmacology, Toxicology and Pharmaceutical Science"=>1}, "Veterinary Science and Veterinary Medicine"=>{"Veterinary Science and Veterinary Medicine"=>2}}, "reader_count_by_country"=>{"United States"=>1, "Denmark"=>1}, "group_count"=>3}

CrossRef

Scopus | Further Information

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