Differential Downregulation of ACE2 by the Spike Proteins of Severe Acute Respiratory Syndrome Coronavirus and Human Coronavirus NL63
Differential Downregulation of ACE2 by the Spike Proteins of Severe Acute Respiratory Syndrome Coronavirus and Human Coronavirus NL63
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DOI：
10.1128/jvi.01248-09
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发表时间：
2010-01-15
影响因子：
5.4
通讯作者：
Poehlmann, Stefan
中科院分区：
文献类型：
--
作者：
Glowacka, Ilona;Bertram, Stephanie;Poehlmann, Stefan
人冠状病毒（CoVs）严重急性呼吸综合征（SARS）-CoV和NL63利用血管紧张素转换酶2（ACE2）进入细胞。研究表明，重组SARS - CoV刺突蛋白（SARS - S）下调ACE2的表达，从而促进肺损伤。NL63 - S是否具有类似的活性尚不清楚。我们发现重组SARS - S与ACE2结合并诱导ACE2脱落的效率高于NL63 - S。脱落很可能是先前观察到的ACE2下调的原因，但对病毒复制并非必需。最后，SARS - CoV而非NL63能在ACE2阳性的Vero细胞中高效复制并降低ACE2的表达，这表明在SARS - CoV感染而非NL63感染的情况下存在强烈的受体干扰。
The human coronaviruses (CoVs) severe acute respiratory syndrome (SARS)-CoV and NL63 employ angiotensin-converting enzyme 2 (ACE2) for cell entry. It was shown that recombinant SARS-CoV spike protein (SARS-S) downregulates ACE2 expression and thereby promotes lung injury. Whether NL63-S exerts a similar activity is yet unknown. We found that recombinant SARS-S bound to ACE2 and induced ACE2 shedding with higher efficiency than NL63-S. Shedding most likely accounted for the previously observed ACE2 down-regulation but was dispensable for viral replication. Finally, SARS-CoV but not NL63 replicated efficiently in ACE2-positive Vero cells and reduced ACE2 expression, indicating robust receptor interference in the context of SARS-CoV but not NL63 infection.