Journal article
Severe acute respiratory syndrome coronavirus infection causes neuronal death in the absence of encephalitis in mice transgenic for human ACE2
Journal of virology, Vol.82(15), pp.7264-7275
08/2008
DOI: 10.1128/JVI.00737-08
PMCID: PMC2493326
PMID: 18495771
Abstract
Infection of humans with the severe acute respiratory syndrome coronavirus (SARS-CoV) results in substantial morbidity and mortality, with death resulting primarily from respiratory failure. While the lungs are the major site of infection, the brain is also infected in some patients. Brain infection may result in long-term neurological sequelae, but little is known about the pathogenesis of SARS-CoV in this organ. We previously showed that the brain was a major target organ for infection in mice that are transgenic for the SARS-CoV receptor (human angiotensin-converting enzyme 2). Herein, we use these mice to show that virus enters the brain primarily via the olfactory bulb, and infection results in rapid, transneuronal spread to connected areas of the brain. This extensive neuronal infection is the main cause of death because intracranial inoculation with low doses of virus results in a uniformly lethal disease even though little infection is detected in the lungs. Death of the animal likely results from dysfunction and/or death of infected neurons, especially those located in cardiorespiratory centers in the medulla. Remarkably, the virus induces minimal cellular infiltration in the brain. Our results show that neurons are a highly susceptible target for SARS-CoV and that only the absence of the host cell receptor prevents severe murine brain disease.
Details
- Title: Subtitle
- Severe acute respiratory syndrome coronavirus infection causes neuronal death in the absence of encephalitis in mice transgenic for human ACE2
- Creators
- Jason Netland - Interdisciplinary Program in Immunology, University of Iowa,Iowa City, IA 52242, USADavid K MeyerholzSteven MooreMartin CassellStanley Perlman
- Resource Type
- Journal article
- Publication Details
- Journal of virology, Vol.82(15), pp.7264-7275
- DOI
- 10.1128/JVI.00737-08
- PMID
- 18495771
- PMCID
- PMC2493326
- NLM abbreviation
- J Virol
- ISSN
- 0022-538X
- eISSN
- 1098-5514
- Publisher
- United States
- Grant note
- P01 AI060699 / NIAID NIH HHS T32 AI007533 / NIAID NIH HHS
- Language
- English
- Date published
- 08/2008
- Academic Unit
- Microbiology and Immunology; Anatomy and Cell Biology; Stead Family Department of Pediatrics; Pathology; Iowa Neuroscience Institute; Infectious Disease (Pediatrics)
- Record Identifier
- 9983777350502771
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