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

5-Aug-2020 2:50 PM EDT, by Uppsala University

Newswise — Researchers at Uppsala University 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 results are presented in Molecular Systems Biology.

The article presents 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, and reports 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," says Dr Cecilia Lindskog, senior author of the paper and Head Director of the Human Protein Atlas tissue team at Uppsala University.

A full understanding of susceptibility to SARS-CoV-2 infection and its progression to a severe and sometimes deadly disease calls for 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 by Hikmet et al. presents 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.

"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 human body, 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 analysis of 360 normal lung samples from an extended patient cohort was based on the Human Protein Atlas (HPA) resource. Two different antibodies, which were stringently validated, were used.

"The HPA programme 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 published along with the ACE2 paper, Nawijn et al. acknowledge the importance of the study and discuss potential explanations for the low expression in the 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 upregulation 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.

"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.

###

The Human Protein Atlas

The Human Protein Atlas (HPA) programme, based at the Science for Life Laboratory in Stockholm, Sweden, started in 2003. Its aim is to map all the human proteins in cells, tissues and organs using integration of various omics technologies, including antibody-based imaging, mass spectrometry-based proteomics, transcriptomics and systems biology. There is open access to all the data in this knowledge resource, so that scientists in academia and industry alike can freely use the data to explore the human proteome.

The Human Protein Atlas programme, which has already contributed to several thousand publications in the fields of human biology and disease, has been selected by ELIXIR (http://www.elixireurope.org), the European intergovernmental organisation, as a core resource for Europe because of its fundamental importance for a wider life-science community. The HPA consortium is funded by the Knut and Alice Wallenberg Foundation

his 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 results are presented in Molecular Systems Biology.

The article presents 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, and reports 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," says Dr Cecilia Lindskog, senior author of the paper and Head Director of the Human Protein Atlas tissue team at Uppsala University.

A full understanding of susceptibility to SARS-CoV-2 infection and its progression to a severe and sometimes deadly disease calls for 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 by Hikmet et al. presents 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.

"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 human body, 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 analysis of 360 normal lung samples from an extended patient cohort was based on the Human Protein Atlas (HPA) resource. Two different antibodies, which were stringently validated, were used.

"The HPA programme 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 published along with the ACE2 paper, Nawijn et al. acknowledge the importance of the study and discuss potential explanations for the low expression in the 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 upregulation 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.

"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.

###

The Human Protein Atlas

The Human Protein Atlas (HPA) programme, based at the Science for Life Laboratory in Stockholm, Sweden, started in 2003. Its aim is to map all the human proteins in cells, tissues and organs using integration of various omics technologies, including antibody-based imaging, mass spectrometry-based proteomics, transcriptomics and systems biology. There is open access to all the data in this knowledge resource, so that scientists in academia and industry alike can freely use the data to explore the human proteome.

The Human Protein Atlas programme, which has already contributed to several thousand publications in the fields of human biology and disease, has been selected by ELIXIR (http://www.elixireurope.org), the European intergovernmental organisation, as a core resource for Europe because of its fundamental importance for a wider life-science community. The HPA consortium is funded by the Knut and Alice Wallenberg Foundation

SEE ORIGINAL STUDY




Filters close

Showing results

110 of 3395
Newswise: Historical Racial & Ethnic Health Inequities Account for Disproportionate COVID-19 Impact
22-Sep-2020 4:00 PM EDT
Historical Racial & Ethnic Health Inequities Account for Disproportionate COVID-19 Impact
American Thoracic Society (ATS)

A new Viewpoint piece published online in the Annals of the American Thoracic Society examines the ways in which COVID-19 disproportionately impacts historically disadvantaged communities of color in the United States, and how baseline inequalities in our health system are amplified by the pandemic. The authors also discuss potential solutions.

Released: 24-Sep-2020 5:05 PM EDT
In-person college instruction leading to thousands of COVID-19 cases per day in US
University of Washington

Reopening university and college campuses with primarily in-person instruction is associated with a significant increase in cases of COVID-19 in the counties where the schools are located.

Newswise: Some Severe COVID-19 Cases Linked to Genetic Mutations or Antibodies that Attack the Body
Released: 24-Sep-2020 3:25 PM EDT
Some Severe COVID-19 Cases Linked to Genetic Mutations or Antibodies that Attack the Body
Howard Hughes Medical Institute (HHMI)

Two new studies offer an explanation for why COVID-19 cases can be so variable. A subset of patients has mutations in key immunity genes; other patients have auto-antibodies that target the same components of the immune system. Both circumstances could contribute to severe forms of the disease.

access_time Embargo lifts in 2 days
Embargo will expire: 25-Sep-2020 6:30 PM EDT Released to reporters: 24-Sep-2020 3:20 PM EDT

A reporter's PressPass is required to access this story until the embargo expires on 25-Sep-2020 6:30 PM EDT The Newswise PressPass gives verified journalists access to embargoed stories. Please log in to complete a presspass application. If you have not yet registered, please Register. When you fill out the registration form, please identify yourself as a reporter in order to advance to the presspass application form.

17-Sep-2020 1:15 PM EDT
Accuracy of commercial antibody kits for SARS-CoV-2 varies widely
PLOS

There is wide variation in the performance of commercial kits for detecting antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), according to a study published September 24 in the open-access journal PLOS Pathogens by Jonathan Edgeworth and Blair Merrick of Guy’s and St Thomas’ NHS Foundation Trust, Suzanne Pickering and Katie Doores of King's College London, and colleagues. As noted by the authors, the rigorous comparison of antibody testing platforms will inform the deployment of point-of-care technologies in healthcare settings and their use in monitoring SARS-CoV-2 infections.

24-Sep-2020 9:25 AM EDT
Loneliness levels high during COVID-19 lockdown
Newswise Review

During the initial phase of COVID-19 lockdown, rates of loneliness among people in the UK were high and were associated with a number of social and health factors, according to a new study published this week in the open-access journal PLOS ONE by Jenny Groarke of Queen’s University Belfast, UK, and colleagues.

Newswise: Genetic, immunological abnormalities in Type I interferon pathway are risk factors for severe COVID-19
24-Sep-2020 12:35 PM EDT
Genetic, immunological abnormalities in Type I interferon pathway are risk factors for severe COVID-19
Uniformed Services University of the Health Sciences (USU)

Individuals with severe forms of COVID-19 disease can present with compromised type I interferon (IFN) responses based on their genetics, according to results published in two papers today in the journal Science. Type I IFN responses are critical for protecting cells and the body from more severe disease after acute viral infection.

Newswise: Talking Alone: Researchers Use Artificial Intelligence Tools to Predict Loneliness
Released: 24-Sep-2020 1:45 PM EDT
Talking Alone: Researchers Use Artificial Intelligence Tools to Predict Loneliness
University of California San Diego Health

A team led by researchers at University of California San Diego School of Medicine has used artificial intelligence technologies to analyze natural language patterns to discern degrees of loneliness in older adults.


Showing results

110 of 3395

close
1.00863