Neuropathogenesis of Japanese encephalitis in a primate model.
Japanese encephalitis (JE) is a major cause of mortality and morbidity for which there is no treatment. In addition to direct viral cytopathology, the inflammatory response is postulated to contribute to the pathogenesis. Our goal was to determine the contribution of bystander effects and inflammato...
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ftdoajarticles:oai:doaj.org/article:d6326f7282674c41a31312bd2dfd975d 2023-05-15T15:10:54+02:00 Neuropathogenesis of Japanese encephalitis in a primate model. Khin Saw Aye Myint Anja Kipar Richard G Jarman Robert V Gibbons Guey Chuen Perng Brian Flanagan Duangrat Mongkolsirichaikul Yvonne Van Gessel Tom Solomon 2014-08-01T00:00:00Z https://doi.org/10.1371/journal.pntd.0002980 https://doaj.org/article/d6326f7282674c41a31312bd2dfd975d EN eng Public Library of Science (PLoS) http://europepmc.org/articles/PMC4125110?pdf=render https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0002980 https://doaj.org/article/d6326f7282674c41a31312bd2dfd975d PLoS Neglected Tropical Diseases, Vol 8, Iss 8, p e2980 (2014) Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 article 2014 ftdoajarticles https://doi.org/10.1371/journal.pntd.0002980 2022-12-31T09:49:45Z Japanese encephalitis (JE) is a major cause of mortality and morbidity for which there is no treatment. In addition to direct viral cytopathology, the inflammatory response is postulated to contribute to the pathogenesis. Our goal was to determine the contribution of bystander effects and inflammatory mediators to neuronal cell death.Material from a macaque model was used to characterize the inflammatory response and cytopathic effects of JE virus (JEV). Intranasal JEV infection induced a non-suppurative encephalitis, dominated by perivascular, infiltrates of mostly T cells, alongside endothelial cell activation, vascular damage and blood brain barrier (BBB) leakage; in the adjacent parenchyma there was macrophage infiltration, astrocyte and microglia activation. JEV antigen was mostly in neurons, but there was no correlation between intensity of viral infection and degree of inflammatory response. Apoptotic cell death occurred in both infected and non-infected neurons. Interferon-α, which is a microglial activator, was also expressed by both. Tumour Necrosis Factor-α, inducible nitric oxide synthase and nitrotyrosine were expressed by microglial cells, astrocytes and macrophages. The same cells expressed matrix metalloproteinase (MMP)-2 whilst MMP-9 was expressed by neurons.The results are consistent with JEV inducing neuronal apoptotic death and release of cytokines that initiate microglial activation and release of pro-inflammatory and apoptotic mediators with subsequent apoptotic death of both infected and uninfected neurons. Activation of astrocytes, microglial and endothelial cells likely contributes to inflammatory cell recruitment and BBB breakdown. It appears that neuronal apoptotic death and activation of microglial cells and astrocytes play a crucial role in the pathogenesis of JE. Article in Journal/Newspaper Arctic Directory of Open Access Journals: DOAJ Articles Arctic PLoS Neglected Tropical Diseases 8 8 e2980 |
institution |
Open Polar |
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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 Khin Saw Aye Myint Anja Kipar Richard G Jarman Robert V Gibbons Guey Chuen Perng Brian Flanagan Duangrat Mongkolsirichaikul Yvonne Van Gessel Tom Solomon Neuropathogenesis of Japanese encephalitis in a primate model. |
topic_facet |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
description |
Japanese encephalitis (JE) is a major cause of mortality and morbidity for which there is no treatment. In addition to direct viral cytopathology, the inflammatory response is postulated to contribute to the pathogenesis. Our goal was to determine the contribution of bystander effects and inflammatory mediators to neuronal cell death.Material from a macaque model was used to characterize the inflammatory response and cytopathic effects of JE virus (JEV). Intranasal JEV infection induced a non-suppurative encephalitis, dominated by perivascular, infiltrates of mostly T cells, alongside endothelial cell activation, vascular damage and blood brain barrier (BBB) leakage; in the adjacent parenchyma there was macrophage infiltration, astrocyte and microglia activation. JEV antigen was mostly in neurons, but there was no correlation between intensity of viral infection and degree of inflammatory response. Apoptotic cell death occurred in both infected and non-infected neurons. Interferon-α, which is a microglial activator, was also expressed by both. Tumour Necrosis Factor-α, inducible nitric oxide synthase and nitrotyrosine were expressed by microglial cells, astrocytes and macrophages. The same cells expressed matrix metalloproteinase (MMP)-2 whilst MMP-9 was expressed by neurons.The results are consistent with JEV inducing neuronal apoptotic death and release of cytokines that initiate microglial activation and release of pro-inflammatory and apoptotic mediators with subsequent apoptotic death of both infected and uninfected neurons. Activation of astrocytes, microglial and endothelial cells likely contributes to inflammatory cell recruitment and BBB breakdown. It appears that neuronal apoptotic death and activation of microglial cells and astrocytes play a crucial role in the pathogenesis of JE. |
format |
Article in Journal/Newspaper |
author |
Khin Saw Aye Myint Anja Kipar Richard G Jarman Robert V Gibbons Guey Chuen Perng Brian Flanagan Duangrat Mongkolsirichaikul Yvonne Van Gessel Tom Solomon |
author_facet |
Khin Saw Aye Myint Anja Kipar Richard G Jarman Robert V Gibbons Guey Chuen Perng Brian Flanagan Duangrat Mongkolsirichaikul Yvonne Van Gessel Tom Solomon |
author_sort |
Khin Saw Aye Myint |
title |
Neuropathogenesis of Japanese encephalitis in a primate model. |
title_short |
Neuropathogenesis of Japanese encephalitis in a primate model. |
title_full |
Neuropathogenesis of Japanese encephalitis in a primate model. |
title_fullStr |
Neuropathogenesis of Japanese encephalitis in a primate model. |
title_full_unstemmed |
Neuropathogenesis of Japanese encephalitis in a primate model. |
title_sort |
neuropathogenesis of japanese encephalitis in a primate model. |
publisher |
Public Library of Science (PLoS) |
publishDate |
2014 |
url |
https://doi.org/10.1371/journal.pntd.0002980 https://doaj.org/article/d6326f7282674c41a31312bd2dfd975d |
geographic |
Arctic |
geographic_facet |
Arctic |
genre |
Arctic |
genre_facet |
Arctic |
op_source |
PLoS Neglected Tropical Diseases, Vol 8, Iss 8, p e2980 (2014) |
op_relation |
http://europepmc.org/articles/PMC4125110?pdf=render https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0002980 https://doaj.org/article/d6326f7282674c41a31312bd2dfd975d |
op_doi |
https://doi.org/10.1371/journal.pntd.0002980 |
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PLoS Neglected Tropical Diseases |
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8 |
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8 |
container_start_page |
e2980 |
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