Angiotensin-converting enzyme 2 (ACE2) is an entry receptor for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and a regulator of several physiological processes. ACE2 has recently been proposed to be interferon (IFN) inducible, suggesting that SARS-CoV-2 may exploit this phenomenon to enhance viral spread and questioning the efficacy of IFN treatment in coronavirus disease 2019. Using a recent de novo transcript assembly that captured previously unannotated transcripts, we describe a new isoform of ACE2, generated by co-option of intronic retroelements as promoter and alternative exon. The new transcript, termed MIRb-ACE2, exhibits specific expression patterns across the aerodigestive and gastrointestinal tracts and is highly responsive to IFN stimulation. In contrast, canonical ACE2 expression is unresponsive to IFN stimulation. Moreover, the MIRb-ACE2 translation product is a truncated, unstable ACE2 form, lacking domains required for SARS-CoV-2 binding and is therefore unlikely to contribute to or enhance viral infection.

血管紧张素转换酶 2 (ACE2) 是严重急性呼吸综合征冠状病毒 2 (SARS-CoV-2) 的进入受体，是多种生理过程的调节剂。ACE2最近被提出是干扰素 (IFN) 诱导的，这表明 SARS-CoV-2 可能利用这种现象来增强病毒传播并质疑 IFN 治疗 2019 年冠状病毒病的疗效。使用最近捕获的从头转录本组装在未注释的转录本中，我们描述了一种新的ACE2同种型，它是通过将内含子逆转录元件共同选择为启动子和替代外显子而产生的。新的转录本，称为MIRb-ACE2，在呼吸消化道和胃肠道中表现出特定的表达模式，并且对 IFN 刺激高度敏感。相比之下，典型的ACE2表达对 IFN 刺激无反应。此外，MIRb-ACE2翻译产物是一种截短的、不稳定的 ACE2 形式，缺乏 SARS-CoV-2 结合所需的结构域，因此不太可能促进或增强病毒感染。