Lethal infection of K18-hACE2 mice infected with severe acute respiratory syndrome coronavirus

Paul B McCray Jr; Lecia Pewe; Christine Wohlford-Lenane; Melissa Hickey; Lori Manzel; Lei Shi; Jason Netland; Hong Peng Jia; Carmen Halabi; Curt D Sigmund; David K Meyerholz; Patricia Kirby; Dwight C Look; Stanley Perlman

doi:10.1128/JVI.02012-06

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Lethal infection of K18-hACE2 mice infected with severe acute respiratory syndrome coronavirus

Journal article

Open access

Peer reviewed

Lethal infection of K18-hACE2 mice infected with severe acute respiratory syndrome coronavirus

Paul B McCray Jr, Lecia Pewe, Christine Wohlford-Lenane, Melissa Hickey, Lori Manzel, Lei Shi, Jason Netland, Hong Peng Jia, Carmen Halabi, Curt D Sigmund, …

Journal of virology, Vol.81(2), pp.813-821

01/2007

DOI: 10.1128/JVI.02012-06

PMCID: PMC1797474

PMID: 17079315

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https://europepmc.org/articles/pmc1797474View

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Abstract

The severe acute respiratory syndrome (SARS), caused by a novel coronavirus (SARS-CoV), resulted in substantial morbidity, mortality, and economic losses during the 2003 epidemic. While SARS-CoV infection has not recurred to a significant extent since 2003, it still remains a potential threat. Understanding of SARS and development of therapeutic approaches have been hampered by the absence of an animal model that mimics the human disease and is reproducible. Here we show that transgenic mice that express the SARS-CoV receptor (human angiotensin-converting enzyme 2 [hACE2]) in airway and other epithelia develop a rapidly lethal infection after intranasal inoculation with a human strain of the virus. Infection begins in airway epithelia, with subsequent alveolar involvement and extrapulmonary virus spread to the brain. Infection results in macrophage and lymphocyte infiltration in the lungs and upregulation of proinflammatory cytokines and chemokines in both the lung and the brain. This model of lethal infection with SARS-CoV should be useful for studies of pathogenesis and for the development of antiviral therapies.

Brain - cytology

Lung - pathology

Severe Acute Respiratory Syndrome - virology

Humans

Mice, Inbred C57BL

Brain - virology

Severe Acute Respiratory Syndrome - mortality

Epithelial Cells - pathology

Mice, Transgenic

Lung - cytology

Keratin-18 - genetics

SARS Virus - pathogenicity

Peptidyl-Dipeptidase A - genetics

Lung - virology

Animals

Keratin-18 - metabolism

Epithelial Cells - virology

Peptidyl-Dipeptidase A - metabolism

Brain - pathology

Mice

Severe Acute Respiratory Syndrome - pathology

Disease Models, Animal

Details

Title: Subtitle: Lethal infection of K18-hACE2 mice infected with severe acute respiratory syndrome coronavirus
Creators: Paul B McCray Jr - Department of Pediatrics, University of Iowa, Iowa City, IA 52242, USA. Paul-McCray@uiowa.edu
Lecia Pewe
Christine Wohlford-Lenane
Melissa Hickey
Lori Manzel
Lei Shi
Jason Netland
Hong Peng Jia
Carmen Halabi
Curt D Sigmund
David K Meyerholz
Patricia Kirby
Dwight C Look
Stanley Perlman
Resource Type: Journal article
Publication Details: Journal of virology, Vol.81(2), pp.813-821
DOI: 10.1128/JVI.02012-06
PMID: 17079315
PMCID: PMC1797474
NLM abbreviation: J Virol
ISSN: 0022-538X
eISSN: 1098-5514
Publisher: United States
Grant note: P01 AI060699-02 / NIAID NIH HHS P30 DK-54759 / NIDDK NIH HHS P01 AI060699 / NIAID NIH HHS P30 DK054759 / NIDDK NIH HHS T32 GM007337 / NIGMS NIH HHS
Language: English
Date published: 01/2007
Academic Unit: Molecular Physiology and Biophysics; Microbiology and Immunology; Pulmonary Medicine; Stead Family Department of Pediatrics; Pathology; Iowa Neuroscience Institute; Neuroscience and Pharmacology; Infectious Disease (Pediatrics)
Record Identifier: 9983777471902771

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