Immunocompetent hamsters as a model for orthobunyavirus-induced neuroinvasion and neuropathology.
Background Bunyavirus infections, including those caused by Bunyamwera serogroup orthobunyaviruses, represent a significant and yet likely still vastly underappreciated cause of mild to moderate human febrile infections. In severe cases, these infections can also cause neurological disease, particul...
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ftdoajarticles:oai:doaj.org/article:cba130ce315848d1a1ebdda07b20dace 2023-07-02T03:31:33+02:00 Immunocompetent hamsters as a model for orthobunyavirus-induced neuroinvasion and neuropathology. Allison Groseth Don Gardner Kimberly Meade-White Susanne Amler Hideki Ebihara 2023-05-01T00:00:00Z https://doi.org/10.1371/journal.pntd.0011355 https://doaj.org/article/cba130ce315848d1a1ebdda07b20dace EN eng Public Library of Science (PLoS) https://doi.org/10.1371/journal.pntd.0011355 https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0011355 https://doaj.org/article/cba130ce315848d1a1ebdda07b20dace PLoS Neglected Tropical Diseases, Vol 17, Iss 5, p e0011355 (2023) Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 article 2023 ftdoajarticles https://doi.org/10.1371/journal.pntd.0011355 2023-06-11T00:37:56Z Background Bunyavirus infections, including those caused by Bunyamwera serogroup orthobunyaviruses, represent a significant and yet likely still vastly underappreciated cause of mild to moderate human febrile infections. In severe cases, these infections can also cause neurological disease, particularly meningitis and encephalitis, and infection can even be fatal. However, with a few exceptions, information regarding the mechanisms underlying the neuroinvasion and neuropathogenesis of such infections is limited. This is due in part to a lack of animal models to facilitate such studies. Methodology/principal findings In an effort to develop an immunocompetent model of infection with Bunyamwera serogroup orthobunyaviruses, we infected 4-6-week-old female hamsters via either the intraperitoneal or subcutaneous route with 106 pfu/animal of Bunyamwera virus (BUNV), Batai virus or Ngari virus. Only BUNV infection resulted in clinical disease, which was characterized by weight loss, lethargy and neurological signs (i.e. tremor of the head or limbs, loss of righting reflex, "waltzing"). While symptoms were of similar severity for both routes, they occurred more frequently following subcutaneous inoculation. Consistent with these clinical signs, both antigen staining and histopathological abnormalities were found extensively throughout the brain. Conclusions/significance The reported hamster model of BUNV infection provides a new tool for studying orthobunyavirus infection, and particularly neuroinvasion and the development of neuropathology. This model is particularly significant because it makes use of immunologically competent animals and relies on a subcutaneous inoculation route that more closely mimics the natural infection route for arboviruses, thereby providing a more authentic cellular and immunological context at the initial site of infection. Article in Journal/Newspaper Arctic Directory of Open Access Journals: DOAJ Articles Arctic PLOS Neglected Tropical Diseases 17 5 e0011355 |
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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 Allison Groseth Don Gardner Kimberly Meade-White Susanne Amler Hideki Ebihara Immunocompetent hamsters as a model for orthobunyavirus-induced neuroinvasion and neuropathology. |
topic_facet |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
description |
Background Bunyavirus infections, including those caused by Bunyamwera serogroup orthobunyaviruses, represent a significant and yet likely still vastly underappreciated cause of mild to moderate human febrile infections. In severe cases, these infections can also cause neurological disease, particularly meningitis and encephalitis, and infection can even be fatal. However, with a few exceptions, information regarding the mechanisms underlying the neuroinvasion and neuropathogenesis of such infections is limited. This is due in part to a lack of animal models to facilitate such studies. Methodology/principal findings In an effort to develop an immunocompetent model of infection with Bunyamwera serogroup orthobunyaviruses, we infected 4-6-week-old female hamsters via either the intraperitoneal or subcutaneous route with 106 pfu/animal of Bunyamwera virus (BUNV), Batai virus or Ngari virus. Only BUNV infection resulted in clinical disease, which was characterized by weight loss, lethargy and neurological signs (i.e. tremor of the head or limbs, loss of righting reflex, "waltzing"). While symptoms were of similar severity for both routes, they occurred more frequently following subcutaneous inoculation. Consistent with these clinical signs, both antigen staining and histopathological abnormalities were found extensively throughout the brain. Conclusions/significance The reported hamster model of BUNV infection provides a new tool for studying orthobunyavirus infection, and particularly neuroinvasion and the development of neuropathology. This model is particularly significant because it makes use of immunologically competent animals and relies on a subcutaneous inoculation route that more closely mimics the natural infection route for arboviruses, thereby providing a more authentic cellular and immunological context at the initial site of infection. |
format |
Article in Journal/Newspaper |
author |
Allison Groseth Don Gardner Kimberly Meade-White Susanne Amler Hideki Ebihara |
author_facet |
Allison Groseth Don Gardner Kimberly Meade-White Susanne Amler Hideki Ebihara |
author_sort |
Allison Groseth |
title |
Immunocompetent hamsters as a model for orthobunyavirus-induced neuroinvasion and neuropathology. |
title_short |
Immunocompetent hamsters as a model for orthobunyavirus-induced neuroinvasion and neuropathology. |
title_full |
Immunocompetent hamsters as a model for orthobunyavirus-induced neuroinvasion and neuropathology. |
title_fullStr |
Immunocompetent hamsters as a model for orthobunyavirus-induced neuroinvasion and neuropathology. |
title_full_unstemmed |
Immunocompetent hamsters as a model for orthobunyavirus-induced neuroinvasion and neuropathology. |
title_sort |
immunocompetent hamsters as a model for orthobunyavirus-induced neuroinvasion and neuropathology. |
publisher |
Public Library of Science (PLoS) |
publishDate |
2023 |
url |
https://doi.org/10.1371/journal.pntd.0011355 https://doaj.org/article/cba130ce315848d1a1ebdda07b20dace |
geographic |
Arctic |
geographic_facet |
Arctic |
genre |
Arctic |
genre_facet |
Arctic |
op_source |
PLoS Neglected Tropical Diseases, Vol 17, Iss 5, p e0011355 (2023) |
op_relation |
https://doi.org/10.1371/journal.pntd.0011355 https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0011355 https://doaj.org/article/cba130ce315848d1a1ebdda07b20dace |
op_doi |
https://doi.org/10.1371/journal.pntd.0011355 |
container_title |
PLOS Neglected Tropical Diseases |
container_volume |
17 |
container_issue |
5 |
container_start_page |
e0011355 |
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1770270926391214080 |