A model of DENV-3 infection that recapitulates severe disease and highlights the importance of IFN-γ in host resistance to infection.
There are few animal models of dengue infection, especially in immunocompetent mice. Here, we describe alterations found in adult immunocompetent mice inoculated with an adapted Dengue virus (DENV-3) strain. Infection of mice with the adapted DENV-3 caused inoculum-dependent lethality that was prece...
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ftdoajarticles:oai:doaj.org/article:cee5995da12c492fba4ab35f8522462e 2023-05-15T15:10:06+02:00 A model of DENV-3 infection that recapitulates severe disease and highlights the importance of IFN-γ in host resistance to infection. Vivian V Costa Caio T Fagundes Deborah F Valadão Daniel Cisalpino Ana Carolina F Dias Kátia D Silveira Lucas M Kangussu Thiago V Ávila Maria Rosa Q Bonfim Daniela Bonaventura Tarcília A Silva Lirlândia P Sousa Milene A Rachid Leda Q Vieira Gustavo B Menezes Ana Maria de Paula Alena Atrasheuskaya George Ignatyev Mauro M Teixeira Danielle G Souza 2012-01-01T00:00:00Z https://doi.org/10.1371/journal.pntd.0001663 https://doaj.org/article/cee5995da12c492fba4ab35f8522462e EN eng Public Library of Science (PLoS) http://europepmc.org/articles/PMC3362616?pdf=render https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0001663 https://doaj.org/article/cee5995da12c492fba4ab35f8522462e PLoS Neglected Tropical Diseases, Vol 6, Iss 5, p e1663 (2012) Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 article 2012 ftdoajarticles https://doi.org/10.1371/journal.pntd.0001663 2022-12-31T02:12:18Z There are few animal models of dengue infection, especially in immunocompetent mice. Here, we describe alterations found in adult immunocompetent mice inoculated with an adapted Dengue virus (DENV-3) strain. Infection of mice with the adapted DENV-3 caused inoculum-dependent lethality that was preceded by several hematological and biochemical changes and increased virus dissemination, features consistent with severe disease manifestation in humans. IFN-γ expression increased after DENV-3 infection of WT mice and this was preceded by increase in expression of IL-12 and IL-18. In DENV-3-inoculated IFN-γ(-/-) mice, there was enhanced lethality, which was preceded by severe disease manifestation and virus replication. Lack of IFN-γ production was associated with diminished NO-synthase 2 (NOS2) expression and higher susceptibility of NOS2(-/-) mice to DENV-3 infection. Therefore, mechanisms of protection to DENV-3 infection rely on IFN-γ-NOS2-NO-dependent control of viral replication and of disease severity, a pathway showed to be relevant for resistance to DENV infection in other experimental and clinical settings. Thus, the model of DENV-3 infection in immunocompetent mice described here represents a significant advance in animal models of severe dengue disease and may provide an important tool to the elucidation of immunopathogenesis of disease and of protective mechanisms associated with infection. Article in Journal/Newspaper Arctic Directory of Open Access Journals: DOAJ Articles Arctic PLoS Neglected Tropical Diseases 6 5 e1663 |
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Open Polar |
collection |
Directory of Open Access Journals: DOAJ Articles |
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ftdoajarticles |
language |
English |
topic |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
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Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 Vivian V Costa Caio T Fagundes Deborah F Valadão Daniel Cisalpino Ana Carolina F Dias Kátia D Silveira Lucas M Kangussu Thiago V Ávila Maria Rosa Q Bonfim Daniela Bonaventura Tarcília A Silva Lirlândia P Sousa Milene A Rachid Leda Q Vieira Gustavo B Menezes Ana Maria de Paula Alena Atrasheuskaya George Ignatyev Mauro M Teixeira Danielle G Souza A model of DENV-3 infection that recapitulates severe disease and highlights the importance of IFN-γ in host resistance to infection. |
topic_facet |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
description |
There are few animal models of dengue infection, especially in immunocompetent mice. Here, we describe alterations found in adult immunocompetent mice inoculated with an adapted Dengue virus (DENV-3) strain. Infection of mice with the adapted DENV-3 caused inoculum-dependent lethality that was preceded by several hematological and biochemical changes and increased virus dissemination, features consistent with severe disease manifestation in humans. IFN-γ expression increased after DENV-3 infection of WT mice and this was preceded by increase in expression of IL-12 and IL-18. In DENV-3-inoculated IFN-γ(-/-) mice, there was enhanced lethality, which was preceded by severe disease manifestation and virus replication. Lack of IFN-γ production was associated with diminished NO-synthase 2 (NOS2) expression and higher susceptibility of NOS2(-/-) mice to DENV-3 infection. Therefore, mechanisms of protection to DENV-3 infection rely on IFN-γ-NOS2-NO-dependent control of viral replication and of disease severity, a pathway showed to be relevant for resistance to DENV infection in other experimental and clinical settings. Thus, the model of DENV-3 infection in immunocompetent mice described here represents a significant advance in animal models of severe dengue disease and may provide an important tool to the elucidation of immunopathogenesis of disease and of protective mechanisms associated with infection. |
format |
Article in Journal/Newspaper |
author |
Vivian V Costa Caio T Fagundes Deborah F Valadão Daniel Cisalpino Ana Carolina F Dias Kátia D Silveira Lucas M Kangussu Thiago V Ávila Maria Rosa Q Bonfim Daniela Bonaventura Tarcília A Silva Lirlândia P Sousa Milene A Rachid Leda Q Vieira Gustavo B Menezes Ana Maria de Paula Alena Atrasheuskaya George Ignatyev Mauro M Teixeira Danielle G Souza |
author_facet |
Vivian V Costa Caio T Fagundes Deborah F Valadão Daniel Cisalpino Ana Carolina F Dias Kátia D Silveira Lucas M Kangussu Thiago V Ávila Maria Rosa Q Bonfim Daniela Bonaventura Tarcília A Silva Lirlândia P Sousa Milene A Rachid Leda Q Vieira Gustavo B Menezes Ana Maria de Paula Alena Atrasheuskaya George Ignatyev Mauro M Teixeira Danielle G Souza |
author_sort |
Vivian V Costa |
title |
A model of DENV-3 infection that recapitulates severe disease and highlights the importance of IFN-γ in host resistance to infection. |
title_short |
A model of DENV-3 infection that recapitulates severe disease and highlights the importance of IFN-γ in host resistance to infection. |
title_full |
A model of DENV-3 infection that recapitulates severe disease and highlights the importance of IFN-γ in host resistance to infection. |
title_fullStr |
A model of DENV-3 infection that recapitulates severe disease and highlights the importance of IFN-γ in host resistance to infection. |
title_full_unstemmed |
A model of DENV-3 infection that recapitulates severe disease and highlights the importance of IFN-γ in host resistance to infection. |
title_sort |
model of denv-3 infection that recapitulates severe disease and highlights the importance of ifn-γ in host resistance to infection. |
publisher |
Public Library of Science (PLoS) |
publishDate |
2012 |
url |
https://doi.org/10.1371/journal.pntd.0001663 https://doaj.org/article/cee5995da12c492fba4ab35f8522462e |
geographic |
Arctic |
geographic_facet |
Arctic |
genre |
Arctic |
genre_facet |
Arctic |
op_source |
PLoS Neglected Tropical Diseases, Vol 6, Iss 5, p e1663 (2012) |
op_relation |
http://europepmc.org/articles/PMC3362616?pdf=render https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0001663 https://doaj.org/article/cee5995da12c492fba4ab35f8522462e |
op_doi |
https://doi.org/10.1371/journal.pntd.0001663 |
container_title |
PLoS Neglected Tropical Diseases |
container_volume |
6 |
container_issue |
5 |
container_start_page |
e1663 |
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1766341154442313728 |