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000284095 0247_ $$2ISSN$$a1432-1831
000284095 0247_ $$2ISSN$$a2199-2983
000284095 037__ $$aDZNE-2026-00103
000284095 041__ $$aEnglish
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000284095 1001_ $$aCosta, Vivian V.$$b0
000284095 245__ $$aSubversion of early innate antiviral responses during antibody-dependent enhancement of Dengue virus infection induces severe disease in immunocompetent mice
000284095 260__ $$aHeidelberg$$bSpringer$$c2014
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000284095 520__ $$aDengue is a mosquito-borne disease caused by one of four serotypes of Dengue virus (DENV-1-4). Epidemiologic and observational studies demonstrate that the majority of severe dengue cases, dengue hemorrhagic fever and dengue shock syndrome (DHF/DSS), occurs predominantly in either individuals with cross-reactive immunity following a secondary heterologous infection or in infants with primary DENV infections born from dengue-immune mothers, suggesting that B-cell-mediated and antibody responses impact on disease evolution. We demonstrate here that B cells play a pivotal role in host responses against primary DENV infection in mice. After infection, μMT(-/-) mice showed increased viral loads followed by severe disease manifestation characterized by intense thrombocytopenia, hemoconcentration, cytokine production and massive liver damage that culminated in death. In addition, we show that poly and monoclonal anti-DENV-specific antibodies can sufficiently increase viral replication through a suppression of early innate antiviral responses and enhance disease manifestation, so that a mostly non-lethal illness becomes a fatal disease resembling human DHF/DSS. Finally, treatment with intravenous immunoglobulin containing anti-DENV antibodies confirmed the potential enhancing capacity of subneutralizing antibodies to mediate virus infection and replication and induce severe disease manifestation of DENV-infected mice. Thus, our results show that humoral responses unleashed during DENV infections can exert protective or pathological outcomes and provide insight into the pathogenesis of this important human pathogen.
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000284095 650_7 $$2NLM Chemicals$$aCytokines
000284095 650_2 $$2MeSH$$aAnimals
000284095 650_2 $$2MeSH$$aAntibody-Dependent Enhancement
000284095 650_2 $$2MeSH$$aB-Lymphocytes: immunology
000284095 650_2 $$2MeSH$$aCytokines: blood
000284095 650_2 $$2MeSH$$aDeath
000284095 650_2 $$2MeSH$$aDengue: immunology
000284095 650_2 $$2MeSH$$aDengue: pathology
000284095 650_2 $$2MeSH$$aDengue Virus: immunology
000284095 650_2 $$2MeSH$$aImmunity, Innate
000284095 650_2 $$2MeSH$$aLiver: pathology
000284095 650_2 $$2MeSH$$aMice, Inbred C57BL
000284095 650_2 $$2MeSH$$aMice, Knockout
000284095 650_2 $$2MeSH$$aThrombocytopenia
000284095 650_2 $$2MeSH$$aViral Load
000284095 7001_ $$aFagundes, Caio T.$$b1
000284095 7001_ $$aValadão, Deborah F.$$b2
000284095 7001_ $$aÁvila, Thiago V.$$b3
000284095 7001_ $$aCisalpino, Daniel$$b4
000284095 7001_ $$aRocha, Rebeca F.$$b5
000284095 7001_ $$0P:(DE-2719)9001782$$aSecchim Ribeiro, Lucas$$b6$$udzne
000284095 7001_ $$aAscenção, Fernando R.$$b7
000284095 7001_ $$aKangussu, Lucas M.$$b8
000284095 7001_ $$aJunior, Celso M. Q.$$b9
000284095 7001_ $$aAstigarraga, Ruiz G.$$b10
000284095 7001_ $$aGouveia, Frederico L.$$b11
000284095 7001_ $$aSilva, Tarcília A.$$b12
000284095 7001_ $$aBonaventura, Daniela$$b13
000284095 7001_ $$ade Almeida Sampaio, Divaldo$$b14
000284095 7001_ $$aLeite, Ana Cristina L.$$b15
000284095 7001_ $$aTeixeira, Mauro M.$$b16
000284095 7001_ $$aSouza, Danielle G.$$b17
000284095 773__ $$0PERI:(DE-600)1462140-X$$a10.1007/s00430-014-0334-5$$gVol. 203, no. 4, p. 231 - 250$$n4$$p231 - 250$$tMedical microbiology and immunology$$v203$$x0300-8584$$y2014
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