In a new study, researchers have described the presence, throughout the human body, of the enzyme ACE2.
This is thought to be the key protein used by the SARS-CoV-2 virus for host cell entry and development of the disease COVID-19.
In contrast to previous studies, the study shows that no or very little ACE2 protein is present in the normal respiratory system.
The research was conducted by a team at Uppsala University.
The team did a large-scale, systematic evaluation of angiotensin I converting enzyme 2 (ACE2) expression in more than 150 cell types, at both messenger RNA (mRNA) and protein levels.
They reported that ACE2 is expressed only at very low levels, if at all, in respiratory epithelial cells.
Considering the clinical manifestations of COVID-19, with acute respiratory distress syndrome and extensive damage to the lung parenchyma, the results highlight the need for further study of the biological mechanisms responsible for COVID-19 infection and disease progression.
A full understanding of susceptibility to COVID-19 infection and its progression to a severe and sometimes deadly disease calls for a study of the SARS-CoV-2 entry receptors and their cell-type-specific expression in human tissues, at both mRNA and protein levels.
It has been suggested that SARS-CoV-2 employs the enzyme ACE2 for host cell entry and that penetration of SARS-CoV-2 via this receptor would explain the severe clinical manifestations observed in various tissues and organs, including the respiratory system.
The study shows a comprehensive update on ACE2 expression throughout the human body, at both mRNA and protein levels.
Consistently high expression was found in the intestines, kidney, gallbladder, heart, male reproductive organs, placenta, eye and vascular system.
In the respiratory system, however, expression was limited, and in a subset of cells in a few individuals, there was no or only low expression.
In the study, the team was able to confidently show that no ACE2 protein is present, or that it occurs at only very low levels, in the normal respiratory system.
Recent studies suggest that ACE2 could be an interferon-induced gene, leading to upregulation during SARS-CoV-2 infection.
It is proposed that ACE2 may first enter and infect eye conjunctiva and cells in the upper airways and that this is followed by ACE2 up-regulation due to the antiviral response, enabling the SARS-CoV-2 to spread and infect the lung parenchyma.
It has also been suggested that smoking may increase ACE2 expression in the respiratory system.
The team says further studies need to find out the dynamic regulation of ACE2, and to confirm whether the low ACE2 expression in the human respiratory system is sufficient for COVID-19 infection.
One author of the study is Dr. Cecilia Lindskog, Head Director of the Human Protein Atlas tissue team at Uppsala University.
The study is published in Molecular Systems Biology.
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