Loss in lung volume and changes in the immune response demonstrate disease progression in African green monkeys infected by small-particle aerosol and intratracheal exposure to Nipah virus.
Nipah virus (NiV) is a paramyxovirus (genus Henipavirus) that emerged in the late 1990s in Malaysia and has since been identified as the cause of sporadic outbreaks of severe febrile disease in Bangladesh and India. NiV infection is frequently associated with severe respiratory or neurological disea...
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2017-04-01
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| Series: | PLoS Neglected Tropical Diseases |
| Online Access: | http://europepmc.org/articles/PMC5397074?pdf=render |
| _version_ | 1828472047476408320 |
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| author | Yu Cong Margaret R Lentz Abigail Lara Isis Alexander Christopher Bartos J Kyle Bohannon Dima Hammoud Louis Huzella Peter B Jahrling Krisztina Janosko Catherine Jett Erin Kollins Matthew Lackemeyer Daniel Mollura Dan Ragland Oscar Rojas Jeffrey Solomon Ziyue Xu Vincent Munster Michael R Holbrook |
| author_facet | Yu Cong Margaret R Lentz Abigail Lara Isis Alexander Christopher Bartos J Kyle Bohannon Dima Hammoud Louis Huzella Peter B Jahrling Krisztina Janosko Catherine Jett Erin Kollins Matthew Lackemeyer Daniel Mollura Dan Ragland Oscar Rojas Jeffrey Solomon Ziyue Xu Vincent Munster Michael R Holbrook |
| author_sort | Yu Cong |
| collection | DOAJ |
| description | Nipah virus (NiV) is a paramyxovirus (genus Henipavirus) that emerged in the late 1990s in Malaysia and has since been identified as the cause of sporadic outbreaks of severe febrile disease in Bangladesh and India. NiV infection is frequently associated with severe respiratory or neurological disease in infected humans with transmission to humans through inhalation, contact or consumption of NiV contaminated foods. In the work presented here, the development of disease was investigated in the African Green Monkey (AGM) model following intratracheal (IT) and, for the first time, small-particle aerosol administration of NiV. This study utilized computed tomography (CT) and magnetic resonance imaging (MRI) to temporally assess disease progression. The host immune response and changes in immune cell populations over the course of disease were also evaluated. This study found that IT and small-particle administration of NiV caused similar disease progression, but that IT inoculation induced significant congestion in the lungs while disease following small-particle aerosol inoculation was largely confined to the lower respiratory tract. Quantitative assessment of changes in lung volume found up to a 45% loss in IT inoculated animals. None of the subjects in this study developed overt neurological disease, a finding that was supported by MRI analysis. The development of neutralizing antibodies was not apparent over the 8-10 day course of disease, but changes in cytokine response in all animals and activated CD8+ T cell numbers suggest the onset of cell-mediated immunity. These studies demonstrate that IT and small-particle aerosol infection with NiV in the AGM model leads to a severe respiratory disease devoid of neurological indications. This work also suggests that extending the disease course or minimizing the impact of the respiratory component is critical to developing a model that has a neurological component and more accurately reflects the human condition. |
| first_indexed | 2024-12-11T05:23:26Z |
| format | Article |
| id | doaj.art-914a177e5f30490cb3ccbfa89c90d8ba |
| institution | Directory Open Access Journal |
| issn | 1935-2727 1935-2735 |
| language | English |
| last_indexed | 2024-12-11T05:23:26Z |
| publishDate | 2017-04-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Neglected Tropical Diseases |
| spelling | doaj.art-914a177e5f30490cb3ccbfa89c90d8ba2022-12-22T01:19:38ZengPublic Library of Science (PLoS)PLoS Neglected Tropical Diseases1935-27271935-27352017-04-01114e000553210.1371/journal.pntd.0005532Loss in lung volume and changes in the immune response demonstrate disease progression in African green monkeys infected by small-particle aerosol and intratracheal exposure to Nipah virus.Yu CongMargaret R LentzAbigail LaraIsis AlexanderChristopher BartosJ Kyle BohannonDima HammoudLouis HuzellaPeter B JahrlingKrisztina JanoskoCatherine JettErin KollinsMatthew LackemeyerDaniel MolluraDan RaglandOscar RojasJeffrey SolomonZiyue XuVincent MunsterMichael R HolbrookNipah virus (NiV) is a paramyxovirus (genus Henipavirus) that emerged in the late 1990s in Malaysia and has since been identified as the cause of sporadic outbreaks of severe febrile disease in Bangladesh and India. NiV infection is frequently associated with severe respiratory or neurological disease in infected humans with transmission to humans through inhalation, contact or consumption of NiV contaminated foods. In the work presented here, the development of disease was investigated in the African Green Monkey (AGM) model following intratracheal (IT) and, for the first time, small-particle aerosol administration of NiV. This study utilized computed tomography (CT) and magnetic resonance imaging (MRI) to temporally assess disease progression. The host immune response and changes in immune cell populations over the course of disease were also evaluated. This study found that IT and small-particle administration of NiV caused similar disease progression, but that IT inoculation induced significant congestion in the lungs while disease following small-particle aerosol inoculation was largely confined to the lower respiratory tract. Quantitative assessment of changes in lung volume found up to a 45% loss in IT inoculated animals. None of the subjects in this study developed overt neurological disease, a finding that was supported by MRI analysis. The development of neutralizing antibodies was not apparent over the 8-10 day course of disease, but changes in cytokine response in all animals and activated CD8+ T cell numbers suggest the onset of cell-mediated immunity. These studies demonstrate that IT and small-particle aerosol infection with NiV in the AGM model leads to a severe respiratory disease devoid of neurological indications. This work also suggests that extending the disease course or minimizing the impact of the respiratory component is critical to developing a model that has a neurological component and more accurately reflects the human condition.http://europepmc.org/articles/PMC5397074?pdf=render |
| spellingShingle | Yu Cong Margaret R Lentz Abigail Lara Isis Alexander Christopher Bartos J Kyle Bohannon Dima Hammoud Louis Huzella Peter B Jahrling Krisztina Janosko Catherine Jett Erin Kollins Matthew Lackemeyer Daniel Mollura Dan Ragland Oscar Rojas Jeffrey Solomon Ziyue Xu Vincent Munster Michael R Holbrook Loss in lung volume and changes in the immune response demonstrate disease progression in African green monkeys infected by small-particle aerosol and intratracheal exposure to Nipah virus. PLoS Neglected Tropical Diseases |
| title | Loss in lung volume and changes in the immune response demonstrate disease progression in African green monkeys infected by small-particle aerosol and intratracheal exposure to Nipah virus. |
| title_full | Loss in lung volume and changes in the immune response demonstrate disease progression in African green monkeys infected by small-particle aerosol and intratracheal exposure to Nipah virus. |
| title_fullStr | Loss in lung volume and changes in the immune response demonstrate disease progression in African green monkeys infected by small-particle aerosol and intratracheal exposure to Nipah virus. |
| title_full_unstemmed | Loss in lung volume and changes in the immune response demonstrate disease progression in African green monkeys infected by small-particle aerosol and intratracheal exposure to Nipah virus. |
| title_short | Loss in lung volume and changes in the immune response demonstrate disease progression in African green monkeys infected by small-particle aerosol and intratracheal exposure to Nipah virus. |
| title_sort | loss in lung volume and changes in the immune response demonstrate disease progression in african green monkeys infected by small particle aerosol and intratracheal exposure to nipah virus |
| url | http://europepmc.org/articles/PMC5397074?pdf=render |
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