論文 - 詳細
| RRC ID | 43365 |
|---|---|
| 著者 | Haga S, Yamamoto N, Nakai-Murakami C, Osawa Y, Tokunaga K, Sata T, Yamamoto N, Sasazuki T, Ishizaka Y. |
| タイトル | Modulation of TNF-alpha-converting enzyme by the spike protein of SARS-CoV and ACE2 induces TNF-alpha production and facilitates viral entry. |
| ジャーナル | Proc Natl Acad Sci U S A |
| Abstract |
Severe acute respiratory syndrome coronavirus (SARS-CoV) is a high-risk infectious pathogen. In the proposed model of respiratory failure, SARS-CoV down-regulates its receptor, angiotensin-converting enzyme 2 (ACE2), but the mechanism involved is unknown. We found that the spike protein of SARS-CoV (SARS-S) induced TNF-alpha-converting enzyme (TACE)-dependent shedding of the ACE2 ectodomain. The modulation of TACE activity by SARS-S depended on the cytoplasmic domain of ACE2, because deletion mutants of ACE2 lacking the carboxyl-terminal region did not induce ACE2 shedding or TNF-alpha production. In contrast, the spike protein of HNL63-CoV (NL63-S), a CoV that uses ACE2 as a receptor and mainly induces the common cold, caused neither of these cellular responses. Intriguingly, viral infection, judged by real-time RT-PCR analysis of SARS-CoV mRNA expression, was significantly attenuated by deletion of the cytoplasmic tail of ACE2 or knock-down of TACE expression by siRNA. These data suggest that cellular signals triggered by the interaction of SARS-CoV with ACE2 are positively involved in viral entry but lead to tissue damage. These findings may lead to the development of anti-SARS-CoV agents. |
| 巻・号 | 105(22) |
| ページ | 7809-14 |
| 公開日 | 2008-6-3 |
| DOI | 10.1073/pnas.0711241105 |
| PII | 0711241105 |
| PMID | 18490652 |
| PMC | PMC2409424 |
| MeSH | ADAM Proteins / metabolism* ADAM17 Protein Angiotensin-Converting Enzyme 2 Animals Cell Line Humans Membrane Glycoproteins / metabolism* Mice Peptidyl-Dipeptidase A / genetics Peptidyl-Dipeptidase A / metabolism* Protein Structure, Tertiary / genetics RNA, Messenger / metabolism RNA, Small Interfering / genetics Sequence Deletion Severe acute respiratory syndrome-related coronavirus / genetics Severe acute respiratory syndrome-related coronavirus / physiology* Spike Glycoprotein, Coronavirus Tumor Necrosis Factor-alpha / metabolism* Viral Envelope Proteins / metabolism* Virus Internalization* |
| IF | 9.412 |
| 引用数 | 95 |
| WOS 分野 | BIOCHEMISTRY & MOLECULAR BIOLOGY |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 99 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| ヒト・動物細胞 | 293T(RCB2202) |