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
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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