Source:http://linkedlifedata.com/resource/pubmed/id/18801550
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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
1
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pubmed:dateCreated |
2008-10-28
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pubmed:abstractText |
Angiotensin converting enzyme 2 (ACE2) is the receptor that severe acute respiratory syndrome coronavirus (SARS-CoV) utilizes for target cell entry and, therefore, plays an important role in SARS pathogenesis. Since Chinese rhesus (rh) macaques do not usually develop SARS after SARS-CoV infection, it has been suggested that rh-ACE2 probably does not support viral entry efficiently. To determine the role of rh-ACE2 in early lung pathogenesis in vivo, we studied eleven Chinese rhesus monkeys experimentally infected with a pathogenic SARS-CoV(PUMC01) strain. Rh-ACE2 genes were amplified from all animals by reverse transcription polymerase chain reaction, and their function was studied in vitro using a pseudovirus entry assay. Many natural non-synonymous (NS) changes were found in rh-ACE2 genes. Compared to human (hu) ACE2, thirty-eight consensus NS changes were found in rh-ACE2. Since these changes do not interact with the receptor binding domain of SARS-CoV, rh-ACE2 in general is as effective as human homolog in supporting viral entry. Rh-ACE2, however, is more polymorphic than hu-ACE2. Additional sporadic NS substitutions in clone Rh11-7 reduced the level of rh-ACE2 protein expression and did not support viral entry effectively. Further mutagenesis analysis showed that a natural mutation Y217N dramatically alters ACE2 expression and entry efficiency. Moreover, introduction of the Y217N mutation into hu-ACE2 caused the down-regulation of expression and reduced viral entry efficiency. These results indicate that the Y217N mutation plays a role in modulating SARS-CoV infection. Our results provide insights for understanding the role of rh-ACE2 in SARS lung pathogenesis in a non-human primate model.
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pubmed:grant | |
pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical | |
pubmed:status |
MEDLINE
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pubmed:month |
Nov
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pubmed:issn |
1096-0341
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pubmed:author | |
pubmed:issnType |
Electronic
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pubmed:day |
10
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pubmed:volume |
381
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
89-97
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pubmed:meshHeading |
pubmed-meshheading:18801550-Amino Acid Sequence,
pubmed-meshheading:18801550-Animals,
pubmed-meshheading:18801550-Cell Line,
pubmed-meshheading:18801550-Female,
pubmed-meshheading:18801550-Gene Expression Regulation, Enzymologic,
pubmed-meshheading:18801550-Humans,
pubmed-meshheading:18801550-Lung,
pubmed-meshheading:18801550-Macaca mulatta,
pubmed-meshheading:18801550-Male,
pubmed-meshheading:18801550-Molecular Sequence Data,
pubmed-meshheading:18801550-Mutation,
pubmed-meshheading:18801550-Peptidyl-Dipeptidase A,
pubmed-meshheading:18801550-SARS Virus,
pubmed-meshheading:18801550-Sequence Alignment,
pubmed-meshheading:18801550-Sequence Homology, Amino Acid,
pubmed-meshheading:18801550-Sequence Homology, Nucleic Acid,
pubmed-meshheading:18801550-Severe Acute Respiratory Syndrome,
pubmed-meshheading:18801550-Virus Internalization
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pubmed:year |
2008
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pubmed:articleTitle |
Rhesus angiotensin converting enzyme 2 supports entry of severe acute respiratory syndrome coronavirus in Chinese macaques.
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pubmed:affiliation |
Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences and Peking Union Medical College, No.5, Panjiayuan, Nanli, Chaoyang District, Beijing, China.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't,
Research Support, N.I.H., Extramural
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