The interferon-stimulated exosomal hACE2 potently inhibits SARS-CoV-2 replication through competitively blocking the virus entry

作者：Junsong Zhang, Feng Huang, Baijin Xia, Yaochang Yuan, Fei Yu, Guanwen Wang, Qianyu Chen, Qian Wang, Yuzhuang Li, Rong Li, Zheng Song, Ting Pan, Jingliang Chen, Gen Lu, Hui Zhang · 发表于：Signal Transduction and Targeted Therapy · 年份：2021 · DOI：10.1038/s41392-021-00604-5 · 被引用次数：37 · 研究领域：Extracellular vesicles in disease、SARS-CoV-2 and COVID-19 Research、Animal Virus Infections Studies

Since the outbreak of coronavirus disease 2019 (COVID-19), it has become a global pandemic. The spike (S) protein of etiologic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) specifically recognizes human angiotensin-converting enzyme 2 (hACE2) as its receptor, which is recently identified as an interferon (IFN)-stimulated gene. Here, we find that hACE2 exists on the surface of exosomes released by different cell types, and the expression of exosomal hACE2 is increased by IFNα/β treatment. In particular, exosomal hACE2 can specifically block the cell entry of SARS-CoV-2, subsequently inhibit the replication of SARS-CoV-2 in vitro and ex vivo. Our findings have indicated that IFN is able to upregulate a viral receptor on the exosomes which competitively block the virus entry, exhibiting a potential antiviral strategy.