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.
abstract: 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.
authors.affiliation: NIAID Integrated Research Facility, Ft. Detrick, Frederick, Maryland, United States of America.
authors.forename: Yu
authors.initials: Y
authors.lastname: Cong
authors.affiliation: NIAID Integrated Research Facility, Ft. Detrick, Frederick, Maryland, United States of America.
authors.forename: Margaret R
authors.initials: MR
authors.lastname: Lentz
authors.affiliation: NIAID Integrated Research Facility, Ft. Detrick, Frederick, Maryland, United States of America.
authors.forename: Abigail
authors.initials: A
authors.lastname: Lara
authors.affiliation: NIAID Integrated Research Facility, Ft. Detrick, Frederick, Maryland, United States of America.
authors.forename: Isis
authors.initials: I
authors.lastname: Alexander
authors.affiliation: NIAID Integrated Research Facility, Ft. Detrick, Frederick, Maryland, United States of America.
authors.forename: Christopher
authors.initials: C
authors.lastname: Bartos
authors.affiliation: NIAID Integrated Research Facility, Ft. Detrick, Frederick, Maryland, United States of America.
authors.forename: J Kyle
authors.initials: JK
authors.lastname: Bohannon
authors.affiliation: Center for Infectious Disease Imaging, NIH Clinical Center, Bethesda, Maryland, United States of America.
authors.forename: Dima
authors.initials: D
authors.lastname: Hammoud
authors.affiliation: NIAID Integrated Research Facility, Ft. Detrick, Frederick, Maryland, United States of America.
authors.forename: Louis
authors.initials: L
authors.lastname: Huzella
authors.affiliation: NIAID Integrated Research Facility, Ft. Detrick, Frederick, Maryland, United States of America.|Emerging Viral Pathogen Section, NIAID, Ft. Detrick, Frederick, Maryland, United States of America.
authors.forename: Peter B
authors.initials: PB
authors.lastname: Jahrling
authors.affiliation: NIAID Integrated Research Facility, Ft. Detrick, Frederick, Maryland, United States of America.
authors.forename: Krisztina
authors.initials: K
authors.lastname: Janosko
authors.affiliation: NIAID Integrated Research Facility, Ft. Detrick, Frederick, Maryland, United States of America.
authors.forename: Catherine
authors.initials: C
authors.lastname: Jett
authors.affiliation: NIAID Integrated Research Facility, Ft. Detrick, Frederick, Maryland, United States of America.
authors.forename: Erin
authors.initials: E
authors.lastname: Kollins
authors.affiliation: NIAID Integrated Research Facility, Ft. Detrick, Frederick, Maryland, United States of America.
authors.forename: Matthew
authors.initials: M
authors.lastname: Lackemeyer
authors.affiliation: Center for Infectious Disease Imaging, NIH Clinical Center, Bethesda, Maryland, United States of America.
authors.forename: Daniel
authors.initials: D
authors.lastname: Mollura
authors.affiliation: NIAID Integrated Research Facility, Ft. Detrick, Frederick, Maryland, United States of America.
authors.forename: Dan
authors.initials: D
authors.lastname: Ragland
authors.affiliation: NIAID Integrated Research Facility, Ft. Detrick, Frederick, Maryland, United States of America.
authors.forename: Oscar
authors.initials: O
authors.lastname: Rojas
authors.affiliation: Clinical Research Directorate/Clinical Monitoring Research Program, Leidos Biomedical Research, NCI Campus, Frederick, Maryland, United States of America.
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Solomon
authors.affiliation: Center for Infectious Disease Imaging, NIH Clinical Center, Bethesda, Maryland, United States of America.
authors.forename: Ziyue
authors.initials: Z
authors.lastname: Xu
authors.affiliation: Virus Ecology Unit, Laboratory of Virology, Rocky Mountain Laboratories, NIAID, Hamilton, Montana, United States of America.
authors.forename: Vincent
authors.initials: V
authors.lastname: Munster
authors.affiliation: NIAID Integrated Research Facility, Ft. Detrick, Frederick, Maryland, United States of America.
authors.forename: Michael R
authors.identifier: 0000-0002-0824-2667
authors.initials: MR
authors.lastname: Holbrook
mesh_terms: D000336:Aerosols; D000818:Animals; D001921:Brain / Q000473:pathology* / Q000821:virology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002522:Chlorocebus aethiops / Q000821:virology; D016207:Cytokines / Q000097:blood; D004195:Disease Models, Animal; D018450:Disease Progression; D005260:Female; D045464:Henipavirus Infections / Q000276:immunology* / Q000662:veterinary; D006801:Humans; D007111:Immunity, Cellular; D008168:Lung / Q000473:pathology* / Q000821:virology; D008279:Magnetic Resonance Imaging; D008297:Male; D045405:Nipah Virus; D012367:RNA, Viral / Q000032:analysis; D014057:Tomography, X-Ray Computed
chemical_list: D000336:Aerosols; D016207:Cytokines; D012367:RNA, Viral