New findings on enzymes with important role in SARS-CoV-2 infection



Colorized scanning electron micrograph of a cell (blue) closely contaminated with SARS-CoV-2 virus particles (purple), remoted from a affected person pattern. Image captured on the NIAID Integrated Research Facility (IRF) in Fort Detrick, Maryland. Credit: NIAID

Researchers at Uppsala University have described the presence, all through the human physique, of the enzyme ACE2. This is regarded as the important thing protein utilized by the SARS-CoV-2 virus for host cell entry and growth of the illness COVID-19. In distinction to earlier research, the examine exhibits that no or little or no ACE2 protein is current in the traditional respiratory system. The outcomes are introduced in Molecular Systems Biology.

The article presents a large-scale, systematic analysis of angiotensin I changing enzyme 2 (ACE2) expression in greater than 150 , at each messenger RNA (mRNA) and ranges, and reviews that ACE2 is expressed solely at very low ranges, if in any respect, in respiratory epithelial .

“Considering the clinical manifestations of COVID-19, with 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,” says Dr. Cecilia Lindskog, senior writer of the paper and Head Director of the Human Protein Atlas tissue crew at Uppsala University.

A full understanding of susceptibility to SARS-CoV-2 infection and its development to a extreme and typically lethal illness requires examine of the SARS-CoV-2 entry receptors and their cell-type-specific expression in human tissues, at each mRNA and protein ranges. It has been recommended that SARS-CoV-2 employs the enzyme ACE2 for host cell entry, and that penetration of SARS-CoV-2 through this receptor would clarify the extreme scientific manifestations noticed in numerous tissues and organs, together with the respiratory system.

The examine by Hikmet et al. presents a complete replace on ACE2 expression all through the human physique, at each mRNA and protein ranges. Consistently excessive expression was discovered in the intestines, kidney, gallbladder, coronary heart, male reproductive organs, placenta, eye and vascular system. In the respiratory system, nonetheless, expression was restricted, and in a subset of cells in just a few people there was no or solely low expression.

“Previous studies have indicated that ACE2 protein is highly expressed in the human lung. But these expression profiles have not been reliably presented along with tissues and organs from the entire , or based on several different datasets at mRNA and protein levels,” Lindskog says.

“Here, in contrast to previous studies, we were able to confidently show that no ACE2 protein is present, or that it occurs at only very low levels, in the normal respiratory system.”

Immunohistochemical evaluation of 360 regular lung samples from an prolonged affected person cohort was primarily based on the Human Protein Atlas (HPA) useful resource. Two totally different antibodies, which had been stringently validated, had been used.

“The HPA program has devoted considerable efforts to introducing and implementing a new concept for enhanced validation of antibodies, using strategies recommended by the International Working Group for Antibody Validation (IWGAV). Such strategies are crucial for determining whether the antibody staining corresponds to true protein expression,” says Professor Mathias Uhlén, Director of the HPA consortium and co-author of the paper.

In a News & Views article printed alongside with the ACE2 paper, Nawijn et al. acknowledge the significance of the examine and focus on potential explanations for the low expression in the respiratory system. Recent research recommend that ACE2 could possibly be an interferon-induced gene, resulting in upregulation throughout SARS-CoV-2 infection. It is proposed that ACE2 could first enter and infect eye conjunctiva and cells in the higher airways, and that that is adopted by ACE2 upregulation because of the antiviral response, enabling the SARS-CoV-2 to unfold and infect the lung parenchyma. It has additionally been recommended that smoking could enhance ACE2 expression in the respiratory system.

“Further studies addressing the dynamic regulation of ACE2, and to confirm whether the low ACE2 expression in the human respiratory system is sufficient for SARS-CoV-2 infection or whether other factors are needed for host cell entry, are urgently needed,” Lindskog says.

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More data:
Martijn C Nawijn et al. Can ACE 2 expression clarify SARS ‐CoV‐2 infection of the respiratory epithelia in COVID ‐19?, Molecular Systems Biology (2020). DOI: 10.15252/msb.20209841

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Uppsala University

New findings on enzymes with important role in SARS-CoV-2 infection (2020, August 5)
retrieved 5 August 2020

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