Natural History and Pathogenesis of Wild-Type Marburg Virus Infection in STAT2 Knockout Hamsters

Colm Atkins, Jinxin Miao, Birte Kalveram, Terry Juelich, Jennifer K. Smith, David Perez, Lihong Zhang, Jonna L.B. Westover, Arnaud J. Van Wettere, Brian B. Gowen, Zhongde Wang, Alexander Freiberg

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Marburg virus (MARV; family Filoviridae) causes sporadic outbreaks of Marburg hemorrhagic fever in sub-Saharan Africa with case fatality rates reaching 90%. Wild-type filoviruses, including MARV and the closely related Ebola virus, are unable to suppress the type I interferon response in rodents, and therefore require adaptation of the viruses to cause disease in immunocompetent animals. In the current study, we demonstrate that STAT2 knockout Syrian hamsters are susceptible to infection with different wild-type MARV variants. MARV Musoke causes a robust and systemic infection resulting in lethal disease. Histopathological findings share features similar to those observed in human patients and other animal models of filovirus infection. Reverse-transcription polymerase chain reaction analysis of host transcripts shows a dysregulation of the innate immune response. Our results demonstrate that the STAT2 knockout hamster represents a novel small animal model of severe MARV infection and disease without the requirement for virus adaptation.

Original languageEnglish (US)
Pages (from-to)S438-S447
JournalThe Journal of infectious diseases
Volume218
Issue number5
DOIs
StatePublished - Nov 22 2018

Fingerprint

Marburgvirus
Virus Diseases
Natural History
Cricetinae
Infection
Filoviridae
Marburg Virus Disease
Animal Models
Ebolavirus
Viruses
Interferon Type I
Africa South of the Sahara
Mesocricetus
Innate Immunity
Reverse Transcription
Disease Outbreaks
Rodentia
Polymerase Chain Reaction
Mortality

ASJC Scopus subject areas

  • Immunology and Allergy
  • Infectious Diseases

Cite this

Natural History and Pathogenesis of Wild-Type Marburg Virus Infection in STAT2 Knockout Hamsters. / Atkins, Colm; Miao, Jinxin; Kalveram, Birte; Juelich, Terry; Smith, Jennifer K.; Perez, David; Zhang, Lihong; Westover, Jonna L.B.; Van Wettere, Arnaud J.; Gowen, Brian B.; Wang, Zhongde; Freiberg, Alexander.

In: The Journal of infectious diseases, Vol. 218, No. 5, 22.11.2018, p. S438-S447.

Research output: Contribution to journalArticle

Atkins, C, Miao, J, Kalveram, B, Juelich, T, Smith, JK, Perez, D, Zhang, L, Westover, JLB, Van Wettere, AJ, Gowen, BB, Wang, Z & Freiberg, A 2018, 'Natural History and Pathogenesis of Wild-Type Marburg Virus Infection in STAT2 Knockout Hamsters', The Journal of infectious diseases, vol. 218, no. 5, pp. S438-S447. https://doi.org/10.1093/infdis/jiy457
Atkins, Colm ; Miao, Jinxin ; Kalveram, Birte ; Juelich, Terry ; Smith, Jennifer K. ; Perez, David ; Zhang, Lihong ; Westover, Jonna L.B. ; Van Wettere, Arnaud J. ; Gowen, Brian B. ; Wang, Zhongde ; Freiberg, Alexander. / Natural History and Pathogenesis of Wild-Type Marburg Virus Infection in STAT2 Knockout Hamsters. In: The Journal of infectious diseases. 2018 ; Vol. 218, No. 5. pp. S438-S447.
@article{684791cadf9e474a85d967b7029cdef3,
title = "Natural History and Pathogenesis of Wild-Type Marburg Virus Infection in STAT2 Knockout Hamsters",
abstract = "Marburg virus (MARV; family Filoviridae) causes sporadic outbreaks of Marburg hemorrhagic fever in sub-Saharan Africa with case fatality rates reaching 90{\%}. Wild-type filoviruses, including MARV and the closely related Ebola virus, are unable to suppress the type I interferon response in rodents, and therefore require adaptation of the viruses to cause disease in immunocompetent animals. In the current study, we demonstrate that STAT2 knockout Syrian hamsters are susceptible to infection with different wild-type MARV variants. MARV Musoke causes a robust and systemic infection resulting in lethal disease. Histopathological findings share features similar to those observed in human patients and other animal models of filovirus infection. Reverse-transcription polymerase chain reaction analysis of host transcripts shows a dysregulation of the innate immune response. Our results demonstrate that the STAT2 knockout hamster represents a novel small animal model of severe MARV infection and disease without the requirement for virus adaptation.",
author = "Colm Atkins and Jinxin Miao and Birte Kalveram and Terry Juelich and Smith, {Jennifer K.} and David Perez and Lihong Zhang and Westover, {Jonna L.B.} and {Van Wettere}, {Arnaud J.} and Gowen, {Brian B.} and Zhongde Wang and Alexander Freiberg",
year = "2018",
month = "11",
day = "22",
doi = "10.1093/infdis/jiy457",
language = "English (US)",
volume = "218",
pages = "S438--S447",
journal = "Journal of Infectious Diseases",
issn = "0022-1899",
publisher = "Oxford University Press",
number = "5",

}

TY - JOUR

T1 - Natural History and Pathogenesis of Wild-Type Marburg Virus Infection in STAT2 Knockout Hamsters

AU - Atkins, Colm

AU - Miao, Jinxin

AU - Kalveram, Birte

AU - Juelich, Terry

AU - Smith, Jennifer K.

AU - Perez, David

AU - Zhang, Lihong

AU - Westover, Jonna L.B.

AU - Van Wettere, Arnaud J.

AU - Gowen, Brian B.

AU - Wang, Zhongde

AU - Freiberg, Alexander

PY - 2018/11/22

Y1 - 2018/11/22

N2 - Marburg virus (MARV; family Filoviridae) causes sporadic outbreaks of Marburg hemorrhagic fever in sub-Saharan Africa with case fatality rates reaching 90%. Wild-type filoviruses, including MARV and the closely related Ebola virus, are unable to suppress the type I interferon response in rodents, and therefore require adaptation of the viruses to cause disease in immunocompetent animals. In the current study, we demonstrate that STAT2 knockout Syrian hamsters are susceptible to infection with different wild-type MARV variants. MARV Musoke causes a robust and systemic infection resulting in lethal disease. Histopathological findings share features similar to those observed in human patients and other animal models of filovirus infection. Reverse-transcription polymerase chain reaction analysis of host transcripts shows a dysregulation of the innate immune response. Our results demonstrate that the STAT2 knockout hamster represents a novel small animal model of severe MARV infection and disease without the requirement for virus adaptation.

AB - Marburg virus (MARV; family Filoviridae) causes sporadic outbreaks of Marburg hemorrhagic fever in sub-Saharan Africa with case fatality rates reaching 90%. Wild-type filoviruses, including MARV and the closely related Ebola virus, are unable to suppress the type I interferon response in rodents, and therefore require adaptation of the viruses to cause disease in immunocompetent animals. In the current study, we demonstrate that STAT2 knockout Syrian hamsters are susceptible to infection with different wild-type MARV variants. MARV Musoke causes a robust and systemic infection resulting in lethal disease. Histopathological findings share features similar to those observed in human patients and other animal models of filovirus infection. Reverse-transcription polymerase chain reaction analysis of host transcripts shows a dysregulation of the innate immune response. Our results demonstrate that the STAT2 knockout hamster represents a novel small animal model of severe MARV infection and disease without the requirement for virus adaptation.

UR - http://www.scopus.com/inward/record.url?scp=85057142130&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85057142130&partnerID=8YFLogxK

U2 - 10.1093/infdis/jiy457

DO - 10.1093/infdis/jiy457

M3 - Article

VL - 218

SP - S438-S447

JO - Journal of Infectious Diseases

JF - Journal of Infectious Diseases

SN - 0022-1899

IS - 5

ER -