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@ARTICLE{Costa:284095,
author = {Costa, Vivian V. and Fagundes, Caio T. and Valadão,
Deborah F. and Ávila, Thiago V. and Cisalpino, Daniel and
Rocha, Rebeca F. and Secchim Ribeiro, Lucas and Ascenção,
Fernando R. and Kangussu, Lucas M. and Junior, Celso M. Q.
and Astigarraga, Ruiz G. and Gouveia, Frederico L. and
Silva, Tarcília A. and Bonaventura, Daniela and de Almeida
Sampaio, Divaldo and Leite, Ana Cristina L. and Teixeira,
Mauro M. and Souza, Danielle G.},
title = {{S}ubversion of early innate antiviral responses during
antibody-dependent enhancement of {D}engue virus infection
induces severe disease in immunocompetent mice},
journal = {Medical microbiology and immunology},
volume = {203},
number = {4},
issn = {0300-8584},
address = {Heidelberg},
publisher = {Springer},
reportid = {DZNE-2026-00103},
pages = {231 - 250},
year = {2014},
abstract = {Dengue 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.},
keywords = {Animals / Antibody-Dependent Enhancement / B-Lymphocytes:
immunology / Cytokines: blood / Death / Dengue: immunology /
Dengue: pathology / Dengue Virus: immunology / Immunity,
Innate / Liver: pathology / Mice, Inbred C57BL / Mice,
Knockout / Thrombocytopenia / Viral Load / Cytokines (NLM
Chemicals)},
ddc = {610},
pnm = {899 - ohne Topic (POF4-899)},
pid = {G:(DE-HGF)POF4-899},
typ = {PUB:(DE-HGF)16},
doi = {10.1007/s00430-014-0334-5},
url = {https://pub.dzne.de/record/284095},
}