Consumptive coagulopathy of severe yellow fever occurs independently of hepatocellular tropism and massive hepatic injury

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dc.contributorSistema FMUSP-HC: Faculdade de Medicina da Universidade de São Paulo (FMUSP) e Hospital das Clínicas da FMUSP
dc.contributor.authorBAILEY, Adam L.
dc.contributor.authorI, Liang- Kang
dc.contributor.authorZANELLA, Luiz Gonzaga Francisco de Assis Barros D'Elia
dc.contributor.authorSILVEIRA, Cassia G. T.
dc.contributor.authorHO, Yeh-Li
dc.contributor.authorFOQUET, Lander
dc.contributor.authorBIAL, Greg
dc.contributor.authorMCCUNE, Broc T.
dc.contributor.authorDUARTE-NETO, Amaro Nunes
dc.contributor.authorTHOMAS, Archana
dc.contributor.authorRAUE, Hans-Peter
dc.contributor.authorBYRNES, Kathleen
dc.contributor.authorKALLAS, Esper G.
dc.contributor.authorSLIFKA, Mark K.
dc.contributor.authorDIAMOND, Michael S.
dc.date.accessioned2021-02-18T13:30:29Z
dc.date.available2021-02-18T13:30:29Z
dc.date.issued2020
dc.description.abstractYellow fever (YF) is a mosquito-transmitted viral disease that causes tens of thousands of deaths each year despite the long-standing deployment of an effective vaccine. In its most severe form, YF manifests as a hemorrhagic fever that causes severe damage to visceral organs. Although coagulopathy is a defining feature of severe YF in humans, the mechanism by which it develops remains uncertain. Hepatocytes are a major target of yellow fever virus (YFV) infection, and the coagulopathy in severe YF has long been attributed to massive hepatocyte infection and destruction that results in a defect in clotting factor synthesis. However, when we analyzed blood from Brazilian patients with severe YF, we found high concentrations of plasma D-dimer, a fibrin split product, suggestive of a concurrent consumptive process. To define the relationship between coagulopathy and hepatocellular tropism, we compared infection and disease in Fah(-/-), Rag2(-/-), and Il2r gamma(-/-) mice engrafted with human hepatocytes (hFRG mice) and rhesus macaques using a highly pathogenic African YFV strain. YFV infection of macaques and hFRG mice caused substantial hepatocyte infection, liver damage, and coagulopathy as defined by virological, clinical, and pathological criteria. However, only macaques developed a consumptive coagulopathy whereas YFV-infected hFRG mice did not. Thus, infection of cell types other than hepatocytes likely contributes to the consumptive coagulopathy associated with severe YF in primates and humans. These findings expand our understanding of viral hemorrhagic disease and associated coagulopathy and suggest directions for clinical management of severe YF cases.eng
dc.description.indexMEDLINEeng
dc.description.sponsorshipNational Institutes of Health (NIH)United States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA [R01 AI073755]
dc.description.sponsorshipNIHUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA [R44 AI079898, T32 EB021955]
dc.description.sponsorshipOregon National Primate Research Center NIH [P51 OD011092]
dc.description.sponsorshipFundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP)Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP) [2013/21728-2]
dc.description.sponsorshipSao Paulo Research Foundation (FAPESP)Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP) [2016/01735-2]
dc.identifier.citationPROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, v.117, n.51, p.32648-32656, 2020
dc.identifier.doi10.1073/pnas.2014096117
dc.identifier.issn0027-8424
dc.identifier.urihttps://observatorio.fm.usp.br/handle/OPI/39237
dc.language.isoeng
dc.publisherNATL ACAD SCIENCESeng
dc.relation.ispartofProceedings of the National Academy of Sciences of the United States of America
dc.rightsopenAccesseng
dc.rights.holderCopyright NATL ACAD SCIENCESeng
dc.subjectyellow fever viruseng
dc.subjectcoagulopathyeng
dc.subjectpathogenesiseng
dc.subjectD-dimereng
dc.subjecthepatitiseng
dc.subject.otherhamster mesocricetus-auratuseng
dc.subject.otherebola hemorrhagic-fevereng
dc.subject.otherwest-nile-viruseng
dc.subject.otherendothelial-cellseng
dc.subject.otheranimal-modelseng
dc.subject.othertissue factoreng
dc.subject.otherdengue viruseng
dc.subject.otherinfectioneng
dc.subject.otherstrainseng
dc.subject.otherdeterminantseng
dc.subject.wosMultidisciplinary Scienceseng
dc.titleConsumptive coagulopathy of severe yellow fever occurs independently of hepatocellular tropism and massive hepatic injuryeng
dc.typearticleeng
dc.type.categoryoriginal articleeng
dc.type.versionpublishedVersioneng
dspace.entity.typePublication
hcfmusp.affiliation.countryEstados Unidos
hcfmusp.affiliation.countryisous
hcfmusp.author.externalBAILEY, Adam L.:Washington Univ, Dept Pathol & Immunol, Sch Med, St Louis, MO 63110 USA
hcfmusp.author.externalI, Liang- Kang:Washington Univ, Dept Pathol & Immunol, Sch Med, St Louis, MO 63110 USA
hcfmusp.author.externalFOQUET, Lander:Yecuris Corp, Tualatin, OR 97062 USA
hcfmusp.author.externalBIAL, Greg:Yecuris Corp, Tualatin, OR 97062 USA
hcfmusp.author.externalMCCUNE, Broc T.:Washington Univ, Dept Med, Sch Med, St Louis, MO 63110 USA
hcfmusp.author.externalTHOMAS, Archana:Oregon Hlth & Sci Univ, Oregon Natl Primate Res Ctr, Div Neurosci, Beaverton, OR 97006 USA
hcfmusp.author.externalRAUE, Hans-Peter:Oregon Hlth & Sci Univ, Oregon Natl Primate Res Ctr, Div Neurosci, Beaverton, OR 97006 USA
hcfmusp.author.externalBYRNES, Kathleen:Washington Univ, Dept Pathol & Immunol, Sch Med, St Louis, MO 63110 USA
hcfmusp.author.externalSLIFKA, Mark K.:Oregon Hlth & Sci Univ, Oregon Natl Primate Res Ctr, Div Neurosci, Beaverton, OR 97006 USA
hcfmusp.author.externalDIAMOND, Michael S.:Washington Univ, Dept Pathol & Immunol, Sch Med, St Louis, MO 63110 USA; Washington Univ, Dept Med, Sch Med, St Louis, MO 63110 USA; Washington Univ, Dept Mol Microbiol, Sch Med, St Louis, MO 63110 USA; Washington Univ, Andrew M & Jane M Bursky Ctr Human Immunol & Immu, Sch Med, St Louis, MO 63110 USA
hcfmusp.citation.scopus12
hcfmusp.contributor.author-fmusphcLUIZ GONZAGA FRANCISCO DE ASSIS BARROS D'ELIA ZANELLA
hcfmusp.contributor.author-fmusphcCASSIA GISELE TERRASSANI SILVEIRA
hcfmusp.contributor.author-fmusphcHO YEH LI
hcfmusp.contributor.author-fmusphcAMARO NUNES DUARTE NETO
hcfmusp.contributor.author-fmusphcESPER GEORGES KALLAS
hcfmusp.description.beginpage32648
hcfmusp.description.endpage32656
hcfmusp.description.issue51
hcfmusp.description.volume117
hcfmusp.origemWOS
hcfmusp.origem.pubmed33268494
hcfmusp.origem.scopus2-s2.0-85098152047
hcfmusp.origem.wosWOS:000601315200057
hcfmusp.publisher.cityWASHINGTONeng
hcfmusp.publisher.countryUSAeng
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