Development of a small animal model for deer tick virus pathogenesis mimicking human clinical outcome.
Powassan virus (POWV) is a tick-borne flavivirus that encompasses two genetic lineages, POWV (Lineage I) and deer tick virus (DTV, Lineage II). In recent years, the incidence of reported POWV disease cases has increased, coupled with an expanded geographic range of the DTV tick vector, Ixodes scapul...
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ftdoajarticles:oai:doaj.org/article:a6f60cd15ef14b82b1e14bcb0c6cc02d 2023-05-15T15:14:06+02:00 Development of a small animal model for deer tick virus pathogenesis mimicking human clinical outcome. Meghan E Hermance Charles E Hart Allen T Esterly Erin S Reynolds Jahnavi R Bhaskar Saravanan Thangamani 2020-06-01T00:00:00Z https://doi.org/10.1371/journal.pntd.0008359 https://doaj.org/article/a6f60cd15ef14b82b1e14bcb0c6cc02d EN eng Public Library of Science (PLoS) https://doi.org/10.1371/journal.pntd.0008359 https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0008359 https://doaj.org/article/a6f60cd15ef14b82b1e14bcb0c6cc02d PLoS Neglected Tropical Diseases, Vol 14, Iss 6, p e0008359 (2020) Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 article 2020 ftdoajarticles https://doi.org/10.1371/journal.pntd.0008359 2022-12-31T11:50:06Z Powassan virus (POWV) is a tick-borne flavivirus that encompasses two genetic lineages, POWV (Lineage I) and deer tick virus (DTV, Lineage II). In recent years, the incidence of reported POWV disease cases has increased, coupled with an expanded geographic range of the DTV tick vector, Ixodes scapularis. POWV and DTV are serologically indistinguishable, and it is not known whether clinical manifestations, pathology, or disease outcome differ between the two viruses. Six-week-old male and female BALB/c mice were footpad-inoculated with DTV doses ranging from 101 to 105 FFU. Dose-independent mortality, morbidity, and organ viral loads were observed for mice inoculated with sequentially increasing doses of DTV. By study completion, all surviving mice had cleared their viremias but detectable levels of negative-sense DTV RNA were present in the brain, indicating viral persistence of infectious DTV in the central nervous system. For mice that succumbed to disease, neuropathology revealed meningoencephalitis characterized by microscopic lesions with widespread distribution of viral RNA in the brain. These findings, coupled with the rapid onset of neurological signs of disease and high viral titers in nervous tissue, highlight the neurotropism of DTV in this mouse model. Additionally, disease outcome for DTV-infected mice was not affected by sex, as males and females were equally susceptible to disease. This is the first study to comprehensively characterize the clinical disease outcome in a small animal model across a spectrum of POWV/DTV infection doses. Here, we developed a small animal model for DTV pathogenesis that mimics the manifestations of POWV disease in humans. Since it is currently not known whether DTV and POWV differ in their capacity to cause human disease, the animal model detailed in our study could be utilized in future comparative pathogenesis studies, or as a platform for testing the efficacy of vaccines, and anti-virals. Article in Journal/Newspaper Arctic Directory of Open Access Journals: DOAJ Articles Arctic PLOS Neglected Tropical Diseases 14 6 e0008359 |
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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 Meghan E Hermance Charles E Hart Allen T Esterly Erin S Reynolds Jahnavi R Bhaskar Saravanan Thangamani Development of a small animal model for deer tick virus pathogenesis mimicking human clinical outcome. |
topic_facet |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
description |
Powassan virus (POWV) is a tick-borne flavivirus that encompasses two genetic lineages, POWV (Lineage I) and deer tick virus (DTV, Lineage II). In recent years, the incidence of reported POWV disease cases has increased, coupled with an expanded geographic range of the DTV tick vector, Ixodes scapularis. POWV and DTV are serologically indistinguishable, and it is not known whether clinical manifestations, pathology, or disease outcome differ between the two viruses. Six-week-old male and female BALB/c mice were footpad-inoculated with DTV doses ranging from 101 to 105 FFU. Dose-independent mortality, morbidity, and organ viral loads were observed for mice inoculated with sequentially increasing doses of DTV. By study completion, all surviving mice had cleared their viremias but detectable levels of negative-sense DTV RNA were present in the brain, indicating viral persistence of infectious DTV in the central nervous system. For mice that succumbed to disease, neuropathology revealed meningoencephalitis characterized by microscopic lesions with widespread distribution of viral RNA in the brain. These findings, coupled with the rapid onset of neurological signs of disease and high viral titers in nervous tissue, highlight the neurotropism of DTV in this mouse model. Additionally, disease outcome for DTV-infected mice was not affected by sex, as males and females were equally susceptible to disease. This is the first study to comprehensively characterize the clinical disease outcome in a small animal model across a spectrum of POWV/DTV infection doses. Here, we developed a small animal model for DTV pathogenesis that mimics the manifestations of POWV disease in humans. Since it is currently not known whether DTV and POWV differ in their capacity to cause human disease, the animal model detailed in our study could be utilized in future comparative pathogenesis studies, or as a platform for testing the efficacy of vaccines, and anti-virals. |
format |
Article in Journal/Newspaper |
author |
Meghan E Hermance Charles E Hart Allen T Esterly Erin S Reynolds Jahnavi R Bhaskar Saravanan Thangamani |
author_facet |
Meghan E Hermance Charles E Hart Allen T Esterly Erin S Reynolds Jahnavi R Bhaskar Saravanan Thangamani |
author_sort |
Meghan E Hermance |
title |
Development of a small animal model for deer tick virus pathogenesis mimicking human clinical outcome. |
title_short |
Development of a small animal model for deer tick virus pathogenesis mimicking human clinical outcome. |
title_full |
Development of a small animal model for deer tick virus pathogenesis mimicking human clinical outcome. |
title_fullStr |
Development of a small animal model for deer tick virus pathogenesis mimicking human clinical outcome. |
title_full_unstemmed |
Development of a small animal model for deer tick virus pathogenesis mimicking human clinical outcome. |
title_sort |
development of a small animal model for deer tick virus pathogenesis mimicking human clinical outcome. |
publisher |
Public Library of Science (PLoS) |
publishDate |
2020 |
url |
https://doi.org/10.1371/journal.pntd.0008359 https://doaj.org/article/a6f60cd15ef14b82b1e14bcb0c6cc02d |
geographic |
Arctic |
geographic_facet |
Arctic |
genre |
Arctic |
genre_facet |
Arctic |
op_source |
PLoS Neglected Tropical Diseases, Vol 14, Iss 6, p e0008359 (2020) |
op_relation |
https://doi.org/10.1371/journal.pntd.0008359 https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0008359 https://doaj.org/article/a6f60cd15ef14b82b1e14bcb0c6cc02d |
op_doi |
https://doi.org/10.1371/journal.pntd.0008359 |
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PLOS Neglected Tropical Diseases |
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14 |
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6 |
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e0008359 |
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