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
| Autor: | Dan R. Ragland, Vincent J. Munster, Christopher Bartos, J. Kyle Bohannon, Oscar Rojas, Krisztina Janosko, Margaret R. Lentz, Abigail Lara, Yu Cong, Louis Huzella, Michael R. Holbrook, Dima A. Hammoud, Ziyue Xu, Erin Kollins, Daniel J. Mollura, Isis Alexander, Jeffrey Solomon, Catherine Jett, Peter B. Jahrling, Matthew G. Lackemeyer |
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| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Male Pulmonology Physiology Disease CD8-Positive T-Lymphocytes Pathology and Laboratory Medicine Vascular Medicine Diagnostic Radiology White Blood Cells 0302 clinical medicine Animal Cells Immune Physiology Chlorocebus aethiops Medicine and Health Sciences 030212 general & internal medicine Respiratory system Immune Response Lung Henipavirus Infections Innate Immune System Immunity Cellular Transmission (medicine) T Cells lcsh:Public aspects of medicine Radiology and Imaging Respiratory disease Brain Magnetic Resonance Imaging Pulmonary Imaging 3. Good health Infectious Diseases medicine.anatomical_structure Physical Sciences Disease Progression Cytokines RNA Viral Female Cellular Types Research Article lcsh:Arctic medicine. Tropical medicine lcsh:RC955-962 Materials by Structure Imaging Techniques Immune Cells Materials Science Immunology Hemorrhage Biology Research and Analysis Methods 03 medical and health sciences Immune system Signs and Symptoms Immunity Diagnostic Medicine medicine Animals Humans Aerosols Blood Cells Public Health Environmental and Occupational Health Nipah Virus Outbreak Biology and Life Sciences lcsh:RA1-1270 Cell Biology Molecular Development medicine.disease Disease Models Animal 030104 developmental biology Mixtures Immune System Respiratory Infections Tomography X-Ray Computed Respiratory tract Developmental Biology |
| Zdroj: | PLoS Neglected Tropical Diseases PLoS Neglected Tropical Diseases, Vol 11, Iss 4, p e0005532 (2017) |
| ISSN: | 1935-2735 1935-2727 |
| Popis: | 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. Author summary Nipah virus (NiV) was identified in the late 1990s as the causative agent of severe respiratory and neurological disease in Malaysia and Bangladesh. The virus is transmitted by inhalation, contact or consumption of contaminated material. In this study, our objective was to characterize NiV-induced disease progression in the African Green Monkey model utilizing clinical imaging capabilities. In this work, we also provide the first temporal evaluation of the immune response to infection following NiV infection and the first characterization of disease following aerosol exposure. Here, we found that NiV infection following intratracheal and aerosol exposure lead to a severe respiratory disease and rapid disease course with no overt clinical evidence of neurological disease. Despite the rapid course of disease, changes in the cytokine response and peripheral immune cell populations suggest development of a cell-mediated immune response in the latter stage of disease. While the current model for evaluating NiV infection is useful for testing of medical countermeasures, further work is required to understand how this model can represent human disease. |
| Databáze: | OpenAIRE |
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