The accessible promoter–mediated supplementary effect of ACE2 provides new insight into the tissue tropism of SARS-CoV-2

Abstract

Background：Angiotensin-converting enzyme 2 (ACE2) has been confirmed to be a receptor for the newly discovered severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, cell surface ACE2 expression is reported to be inconsistent with clinical tissue tropism of SARS-CoV-2, which complicates understanding of the pathogenesis of 2019 novel coronavirus disease (COVID-19). The consumption of ACE2 by internalization and shedding processes may explain this discordance. Results：To understand the discordance between ACE2 expression and the tissue tropism of SARS-CoV-2, we examined the chromatin accessibility of ACE2 promoter in hundreds of tissues and cell lines using public DNase-seq and assay for transposase-accessible chromatin with high throughput sequencing (ATAC-seq) data. We find that ACE2 promoter is only accessible in three tissues including lung, large intestine and placenta. Also, we examined tumors tissues and ACE2 promoter is observed accessible in five tumors with reported SARS-CoV-2 susceptibility. We confirmed the susceptibility by performing SARS-CoV-2 pseudovirus infection in several cell lines. Conclusions：We propose that open chromatin at the promoter mediates the ACE2 supplementary effect and ensures the entry of SARS-CoV-2. This hypothesis provides a new view and potential clues for further investigation of COVID-19 pathogenesis.