ACE2 expression by colonic epithelial cells is associated with viral infection, immunity and energy metabolism


Respiratory disease caused by the 2019 novel coronavirus (2019-nCoV) pneumonia first emerged in Wuhan, Hubei Province, China, in December 2019 and spread rapidly to other provinces and other countries. Angiotensin-converting enzyme 2 (ACE2) is the receptor for SARS-CoV and has been suggested to be also the receptor for 2019-nCoV. Paradoxically, ACE2 expression in the lung protects mice from SARS-CoV spike protein induced lung injury by attenuating the renin-angiotensin system. In the intestine, ACE2 also suppresses intestinal inflammation by maintaining amino acid homeostasis, antimicrobial peptide expression and ecology of the gut microbiome. Upon analysis of single cell-RNA sequencing data from control subjects and those with colitis or inflammatory bowel disease (IBD), we found that ACE2 expression in the colonocytes was positively associated with genes regulating viral infection, innate and cellular immunity, but was negatively associated with viral transcription, protein translation, humoral immunity, phagocytosis and complement activation. In summary, we suggest that ACE2 may play dual roles in mediating the susceptibility and immunity of 2019- nCoV infection.

Patients infected by 2019-nCoV can develop acute respiratory distress syndrome (ARDS) and sepsis. However, there is mounting evidences that the gastrointestinal tract may be an alternative All rights reserved. No reuse allowed without permission. author/funder, who has granted medRxiv a license to display the preprint in perpetuity. medRxiv preprint doi: The copyright holder for this preprint (which was not peer-reviewed) is the 3 route for 2019-nCoV infection. One (3%) of the first 41 reported cases had diarrhea. In another report describing a familial cluster, 2 of the 6 family members (33%) developed diarrhea. Furthermore, positive 2019-nCoV was detected from the stools of a patient with loose of bowel movement in the United States. There have been many studies on the proteins associated with host entry by the SARS-CoV. Cleavage of Spike protein by tissue factor Xa is required for the infectivity of SARS-CoV. Rivaroxaban is an oral anticoagulant used to combat acute pulmonary embolism with or without deep-vein thrombosis. As an Xa inhibitor, it may thus offer protection for 2019-nCoV pneumonia. Angiotensin I converting enzyme 2 (ACE2) is the SARS-CoV receptor. It also has been linked to 2019-nCoV infection; ACE2 interacts with the Spike protein and mediates 2019-nCoV infection of the type II alveolar cells of the lung. Paradoxically, although ACE2 mediates viral entry to the host, its deficiency worsens lung injury by activating the renin-angiotensin system (RAS) in experimental models. The circulating RAS regulates blood pressure and fluid homeostasis. Local tissue-based RAS exacerbates pulmonary hypertension, acute lung injury and experimental lung fibrosis. Thus, blocking of the Angiotensin II receptor type I (AT1R) was associated with reduced SARS-CoV spike protein mediated lung injury and reduced pulmonary hypertension in experimental models. The AT1R blocker valsartan has recently been reported to improve clinical outcomes for patients with chronic obstructive pulmonary disease (COPD) complicated with pulmonary hypertension.

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