US, WASHINGTON (ORDO NEWS) —
Scientists from Harvard University and the Massachusetts Institute of Technology have identified cell types that can serve as primary targets for coronavirus entering the body. The results of the study are presented on the website of the laboratory of Alex Shalek, one of the leaders of the study. The article will later be published on Cell .The distribution of a subset of epithelial cells performed using the tSNE algorithm. On the left, the different cell types are shown in different colors. In the right diagram, cell populations expressing large quantities of ACE2 and TMPRSS2 are highlighted in red / © Shalek Lab
Using data on RNA, which is expressed in various cells of the body, scientists have identified those cells in which proteins necessary for the penetration of the virus are expressed in sufficient quantities. Large populations of such cells are found in the nasal passages, lungs, and intestines.
The proteins in question are the ACE2 angiotensin converting enzyme and the TMPRSS2 protease. The first of these molecules plays an important role in cardiac function – in particular, due to the catalysis of reactions of synthesis of substances with a vasodilating effect. As for TMPRSS2, the function of this enzyme in the body is still not exactly understood; its role in the development of certain types of prostate cancer is best known. But it is well known how ACE2 and TMPRSS2 help the SARS-CoV-2 virus infect the host organism. The first protein binds to the spiky proteins of the viral particle, and the second activates these proteins, thereby triggering the mechanism of penetration into the cell.The distribution of cell types of lungs and ileum of the lower primates, which were considered as possible targets for the penetration of coronavirus. The right side shows the place among these cells of those that express ACE2 and TMPRSS2, respectively / © Shalek Lab
“Once we realized that the role of these proteins was biochemically confirmed, we started looking for their genes in our existing data sets,” says study co-author José Ordovas-Montanes.
The employees of the Shalek laboratory, along with scientists in many other scientific institutions, conducted a large-scale study of tens of thousands of different human cells, primates and rodents in order to compile their transcriptional profile. Most of the data was provided by the participants in the Atlas of Human Cells project, which creates a catalog of gene activity patterns for each type of cell in the human body.
Among nasal passage cells, both ACE2 and TMPRSS2 goblet enterocytes are most actively expressed. Their main function is the production of mucus for the epithelium of the mucous membrane. In the lungs, RNA of both proteins was found in large quantities in granular alveolocytes – cells that produce pulmonary surfactant, synthesize immunomodulators and regulate the transport of ions and water through the epithelium. And in the intestine, both proteins are most actively synced in the limbic enterocytes, which make up almost 9/10 of the total number of cells in the villi of the rectum.Distribution of ACE2 + and TMPRSS2 + cells in the small intestine and intestinal organoids of a person / © Shalek Lab
In the course of research, scientists found an unexpected correlation. It turned out that the expression of the ACE2 gene correlates with the expression of genes that are activated by interferon – a substance produced during the immune response to infection.
Experiments in which granular alveolocytes were treated with interferon confirmed this assumption. This suggests that the SARS-CoV-2 virus in the course of its evolution could learn how to use the cell’s defense mechanisms for its own needs. In fact, one of the side effects of the immune response in the case of coronavirus is that it “opens the gate” for infection.
The authors hope that their study will be of great help to scientists who are working on creating new or testing existing anti-virus drugs. “Our goal is to bring information to the [scientific] community and share data as quickly as possible so that we help scientists and doctors,” says Alex Shalek.
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