PMID- 17079315
OWN - NLM
STAT- MEDLINE
DCOM- 20070201
LR  - 20221207
IS  - 0022-538X (Print)
IS  - 1098-5514 (Electronic)
IS  - 0022-538X (Linking)
VI  - 81
IP  - 2
DP  - 2007 Jan
TI  - Lethal infection of K18-hACE2 mice infected with severe acute respiratory 
      syndrome coronavirus.
PG  - 813-21
AB  - 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.
FAU - McCray, Paul B Jr
AU  - McCray PB Jr
AD  - Department of Pediatrics, University of Iowa, Iowa City, IA 52242, USA. 
      Paul-McCray@uiowa.edu
FAU - Pewe, Lecia
AU  - Pewe L
FAU - Wohlford-Lenane, Christine
AU  - Wohlford-Lenane C
FAU - Hickey, Melissa
AU  - Hickey M
FAU - Manzel, Lori
AU  - Manzel L
FAU - Shi, Lei
AU  - Shi L
FAU - Netland, Jason
AU  - Netland J
FAU - Jia, Hong Peng
AU  - Jia HP
FAU - Halabi, Carmen
AU  - Halabi C
FAU - Sigmund, Curt D
AU  - Sigmund CD
FAU - Meyerholz, David K
AU  - Meyerholz DK
FAU - Kirby, Patricia
AU  - Kirby P
FAU - Look, Dwight C
AU  - Look DC
FAU - Perlman, Stanley
AU  - Perlman S
LA  - eng
GR  - P30 DK-54759/DK/NIDDK NIH HHS/United States
GR  - P01 AI060699/AI/NIAID NIH HHS/United States
GR  - P30 DK054759/DK/NIDDK NIH HHS/United States
GR  - T32 GM007337/GM/NIGMS NIH HHS/United States
GR  - P01 AI060699-02/AI/NIAID NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20061101
PL  - United States
TA  - J Virol
JT  - Journal of virology
JID - 0113724
RN  - 0 (Keratin-18)
RN  - EC 3.4.15.1 (Peptidyl-Dipeptidase A)
SB  - IM
MH  - Animals
MH  - Brain/cytology/pathology/virology
MH  - *Disease Models, Animal
MH  - Epithelial Cells/pathology/virology
MH  - Humans
MH  - Keratin-18/genetics/*metabolism
MH  - Lung/cytology/pathology/virology
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Transgenic
MH  - Peptidyl-Dipeptidase A/genetics/*metabolism
MH  - Severe acute respiratory syndrome-related coronavirus/*pathogenicity
MH  - Severe Acute Respiratory Syndrome/mortality/pathology/virology
PMC - PMC1797474
EDAT- 2006/11/03 09:00
MHDA- 2007/02/03 09:00
PMCR- 2007/05/01
CRDT- 2006/11/03 09:00
PHST- 2006/11/03 09:00 [pubmed]
PHST- 2007/02/03 09:00 [medline]
PHST- 2006/11/03 09:00 [entrez]
PHST- 2007/05/01 00:00 [pmc-release]
AID - JVI.02012-06 [pii]
AID - 2012-06 [pii]
AID - 10.1128/JVI.02012-06 [doi]
PST - ppublish
SO  - J Virol. 2007 Jan;81(2):813-21. doi: 10.1128/JVI.02012-06. Epub 2006 Nov 1.