Host gene expression profiles in ferrets infected with genetically distinct henipavirus strains

Alberto J. Leon, Viktoriya Borisevich, Nahal Boroumand, Robert Seymour, Rebecca Nusbaum, Olivier Escaffre, Luoling Xu, David J. Kelvin, Barry Rockx

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Henipavirus infection causes severe respiratory and neurological disease in humans that can be fatal. To characterize the pathogenic mechanisms of henipavirus infection in vivo, we performed experimental infections in ferrets followed by genome-wide gene expression analysis of lung and brain tissues. The Hendra, Nipah-Bangladesh, and Nipah-Malaysia strains caused severe respiratory and neurological disease with animals succumbing around 7 days post infection. Despite the presence of abundant viral shedding, animal-to-animal transmission did not occur. The host gene expression profiles of the lung tissue showed early activation of interferon responses and subsequent expression of inflammation-related genes that coincided with the clinical deterioration. Additionally, the lung tissue showed unchanged levels of lymphocyte markers and progressive downregulation of cell cycle genes and extracellular matrix components. Infection in the brain resulted in a limited breadth of the host responses, which is in accordance with the immunoprivileged status of this organ. Finally, we propose a model of the pathogenic mechanisms of henipavirus infection that integrates multiple components of the host responses.

Original languageEnglish (US)
Article numbere0006343
JournalPLoS Neglected Tropical Diseases
Volume12
Issue number3
DOIs
StatePublished - Mar 14 2018

Fingerprint

Henipavirus Infections
Henipavirus
Ferrets
Transcriptome
Lung
Infection
Virus Shedding
cdc Genes
Animal Diseases
Bangladesh
Malaysia
Brain
Interferons
Extracellular Matrix
Down-Regulation
Genome
Lymphocytes
Inflammation
Gene Expression
Genes

ASJC Scopus subject areas

  • Public Health, Environmental and Occupational Health
  • Infectious Diseases

Cite this

Host gene expression profiles in ferrets infected with genetically distinct henipavirus strains. / Leon, Alberto J.; Borisevich, Viktoriya; Boroumand, Nahal; Seymour, Robert; Nusbaum, Rebecca; Escaffre, Olivier; Xu, Luoling; Kelvin, David J.; Rockx, Barry.

In: PLoS Neglected Tropical Diseases, Vol. 12, No. 3, e0006343, 14.03.2018.

Research output: Contribution to journalArticle

Leon, AJ, Borisevich, V, Boroumand, N, Seymour, R, Nusbaum, R, Escaffre, O, Xu, L, Kelvin, DJ & Rockx, B 2018, 'Host gene expression profiles in ferrets infected with genetically distinct henipavirus strains', PLoS Neglected Tropical Diseases, vol. 12, no. 3, e0006343. https://doi.org/10.1371/journal.pntd.0006343
Leon, Alberto J. ; Borisevich, Viktoriya ; Boroumand, Nahal ; Seymour, Robert ; Nusbaum, Rebecca ; Escaffre, Olivier ; Xu, Luoling ; Kelvin, David J. ; Rockx, Barry. / Host gene expression profiles in ferrets infected with genetically distinct henipavirus strains. In: PLoS Neglected Tropical Diseases. 2018 ; Vol. 12, No. 3.
@article{ffda68f55bb041dd9c95ec949a0509c6,
title = "Host gene expression profiles in ferrets infected with genetically distinct henipavirus strains",
abstract = "Henipavirus infection causes severe respiratory and neurological disease in humans that can be fatal. To characterize the pathogenic mechanisms of henipavirus infection in vivo, we performed experimental infections in ferrets followed by genome-wide gene expression analysis of lung and brain tissues. The Hendra, Nipah-Bangladesh, and Nipah-Malaysia strains caused severe respiratory and neurological disease with animals succumbing around 7 days post infection. Despite the presence of abundant viral shedding, animal-to-animal transmission did not occur. The host gene expression profiles of the lung tissue showed early activation of interferon responses and subsequent expression of inflammation-related genes that coincided with the clinical deterioration. Additionally, the lung tissue showed unchanged levels of lymphocyte markers and progressive downregulation of cell cycle genes and extracellular matrix components. Infection in the brain resulted in a limited breadth of the host responses, which is in accordance with the immunoprivileged status of this organ. Finally, we propose a model of the pathogenic mechanisms of henipavirus infection that integrates multiple components of the host responses.",
author = "Leon, {Alberto J.} and Viktoriya Borisevich and Nahal Boroumand and Robert Seymour and Rebecca Nusbaum and Olivier Escaffre and Luoling Xu and Kelvin, {David J.} and Barry Rockx",
year = "2018",
month = "3",
day = "14",
doi = "10.1371/journal.pntd.0006343",
language = "English (US)",
volume = "12",
journal = "PLoS Neglected Tropical Diseases",
issn = "1935-2727",
publisher = "Public Library of Science",
number = "3",

}

TY - JOUR

T1 - Host gene expression profiles in ferrets infected with genetically distinct henipavirus strains

AU - Leon, Alberto J.

AU - Borisevich, Viktoriya

AU - Boroumand, Nahal

AU - Seymour, Robert

AU - Nusbaum, Rebecca

AU - Escaffre, Olivier

AU - Xu, Luoling

AU - Kelvin, David J.

AU - Rockx, Barry

PY - 2018/3/14

Y1 - 2018/3/14

N2 - Henipavirus infection causes severe respiratory and neurological disease in humans that can be fatal. To characterize the pathogenic mechanisms of henipavirus infection in vivo, we performed experimental infections in ferrets followed by genome-wide gene expression analysis of lung and brain tissues. The Hendra, Nipah-Bangladesh, and Nipah-Malaysia strains caused severe respiratory and neurological disease with animals succumbing around 7 days post infection. Despite the presence of abundant viral shedding, animal-to-animal transmission did not occur. The host gene expression profiles of the lung tissue showed early activation of interferon responses and subsequent expression of inflammation-related genes that coincided with the clinical deterioration. Additionally, the lung tissue showed unchanged levels of lymphocyte markers and progressive downregulation of cell cycle genes and extracellular matrix components. Infection in the brain resulted in a limited breadth of the host responses, which is in accordance with the immunoprivileged status of this organ. Finally, we propose a model of the pathogenic mechanisms of henipavirus infection that integrates multiple components of the host responses.

AB - Henipavirus infection causes severe respiratory and neurological disease in humans that can be fatal. To characterize the pathogenic mechanisms of henipavirus infection in vivo, we performed experimental infections in ferrets followed by genome-wide gene expression analysis of lung and brain tissues. The Hendra, Nipah-Bangladesh, and Nipah-Malaysia strains caused severe respiratory and neurological disease with animals succumbing around 7 days post infection. Despite the presence of abundant viral shedding, animal-to-animal transmission did not occur. The host gene expression profiles of the lung tissue showed early activation of interferon responses and subsequent expression of inflammation-related genes that coincided with the clinical deterioration. Additionally, the lung tissue showed unchanged levels of lymphocyte markers and progressive downregulation of cell cycle genes and extracellular matrix components. Infection in the brain resulted in a limited breadth of the host responses, which is in accordance with the immunoprivileged status of this organ. Finally, we propose a model of the pathogenic mechanisms of henipavirus infection that integrates multiple components of the host responses.

UR - http://www.scopus.com/inward/record.url?scp=85045113716&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85045113716&partnerID=8YFLogxK

U2 - 10.1371/journal.pntd.0006343

DO - 10.1371/journal.pntd.0006343

M3 - Article

VL - 12

JO - PLoS Neglected Tropical Diseases

JF - PLoS Neglected Tropical Diseases

SN - 1935-2727

IS - 3

M1 - e0006343

ER -