Vaccine Branch, Center of Cancer Research, National Cancer Institute, National Institutes of Health (NIH), Bethesda, MD, United States.
Biostatistics and Data Management Section, Center of Cancer Research, National Cancer Institute, National Institutes of Health (NIH), Bethesda, MD, United States.
Front Immunol. 2021 Jun 4;12:658428. doi: 10.3389/fimmu.2021.658428. eCollection 2021.
SARS-CoV-2 virus causes upper and lower respiratory diseases including pneumonia, and in some cases, leads to lethal pulmonary failure. Angiotensin converting enzyme-2 (ACE2), the receptor for cellular entry of SARS-CoV-2 virus, has been shown to protect against severe acute lung failure. Here, we provide evidence that SARS-CoV-2 spike protein S1 reduced the mRNA expression of ACE2 and type I interferons in primary cells of lung bronchoalveolar lavage (BAL) from naïve rhesus macaques. The expression levels of ACE2 and type I interferons were also found to be correlated with each other, consistent with the recent finding that ACE2 is an interferon-inducible gene. Furthermore, induction of ACE2 and type I interferons by poly I:C, an interferon inducer, was suppressed by S1 protein in primary cells of BAL. These observations suggest that the downregulation of ACE2 and type I interferons induced by S1 protein may directly contribute to SARS-CoV-2-associated lung diseases.
严重急性呼吸综合征冠状病毒 2 型（SARS-CoV-2）病毒可引起上呼吸道和下呼吸道疾病，包括肺炎，在某些情况下，还可导致致命性的肺衰竭。血管紧张素转换酶 2（ACE2）是 SARS-CoV-2 病毒进入细胞的受体，已被证明可预防严重急性肺衰竭。在这里，我们提供的证据表明，SARS-CoV-2 刺突蛋白 S1 降低了来自天真恒河猴肺支气管肺泡灌洗液（BAL）的原代细胞中 ACE2 和 I 型干扰素的 mRNA 表达。ACE2 和 I 型干扰素的表达水平也相互关联，这与 ACE2 是干扰素诱导基因的最近发现一致。此外，干扰素诱导剂 poly I:C 诱导的 ACE2 和 I 型干扰素在 BAL 的原代细胞中被 S1 蛋白抑制。这些观察结果表明，S1 蛋白诱导的 ACE2 和 I 型干扰素下调可能直接导致与 SARS-CoV-2 相关的肺部疾病。
