can penetrate the corona virus in our cells, it must bind to a Receptor on the surface of human cells. From previous studies it is already known that this docking site, the so-called Angiotensin-Converting enzyme 2 short ACE2. This Receptor was also used by the closely related Sars Coronavirus cell entry. The Coronavirus doesnt have to be a prominent Envelope protein, the Spike Protein to get up, so that the binding site is free, and it can attach to the ACE2 Receptor. In addition, the Virus is likely to require one or more on the cell membrane at the end of Cofactors, that help him in this, in the host cell to invade. Analyses show that ACE2 in the tissue of the lung, the kidney, the heart and the digestive tract is available, which could explain why Sars-CoV-2 can trigger in some patients diarrhea, and heart problems.
RNA-tracing in pulmonary and bronchial tissue
But what are the cell types of the ACE2 Receptor, as well as the necessary Cofactors, is cleared only in Parts. “We wanted to know which cells are exactly is it that infests the Coronavirus,” explains senior author Christian Conrad, of the Charité Universitätsmedizin Berlin. In order to clarify this, the researchers used tissue samples from the lungs and bronchi of 16 patients who had undergone due to a suspicion of cancer, a biopsy or bronchoscopy. None of the patients was suffering from Covid-19 or with the Coronavirus infected. The researchers studied the samples using the RNA-analysis on copies of the genes encoding the ACE2 Receptor and the cofactor TMPRSS2. In supplementary analyses, you could also narrow down, which carry the cells in the tissues of these factors and how many of them.
“We have investigated a total of almost 60,000 cells to see if they have switches on the genes for the Receptor and any Cofactors, and thus, in principle, from the corona virus can be infected,” says first author Soeren Lukassen of the Charité and the Berlin Institute of Health. The analyses showed that in the lung, especially in the pulmonary alveoli of a sitting type of cell tissues and the ACE2-forming Receptor. These so-called Alveolozyten of the type 2 (AT2) to cover round vesicles, five percent of the inner surface in the lungs, and, above all, ensure that the Breathing important exchange surface between blood vessels and air with a special liquid moistened remains. The AT2 cells showed the highest level of ACE2 Expression in the lungs in terms of both the number as to the percentage of positive cells,” the researchers report. For the other lung cells occurring cofactor TMPRSS2 they also found slightly increased values on the AT2 cells.
cells of the alveoli and bronchial progenitor cells
a Little different the results for the bronchi were: “The most striking result of this study is to demonstrate the ACR2 Expression was the skin of a Population of progenitor cells for the respiratory tract mucus”, reports Lukassen and his colleagues. These precursor cells develop normally to the cells in the respiratory tract, with their cilia that mucus and bacteria are transported out of the lungs. From the current analyses show that this produces both the ACE2 Receptor as well as the cofactor TMPRSS2 in a particularly strong degree. These progenitor cells may therefore be compared with the Sars-CoV-2 infection are particularly vulnerable, as the researchers explain. “These results show us that the Virus is very targeted, and specific cells in the body is dependent, to be able to spread and proliferate,” explains Co-senior author Roland Eils of the Charité and the Berlin Institute of Health.
As an interesting secondary finding, the Team also noted that the density of the ACE2 receptor increases the cells with the age of the patients apparently. In addition, this docking seems to be on the cells of men to be stronger than women. “It was just a Trend, but it could explain why more men than women are infected,” says Eils. “For a verifiable statement of our case numbers, however, are still much too low. In this investigation, we need to repeat in larger patient cohorts.” In the next step, the scientists now want to investigate Covid-19 patients to determine whether in fact these cells are Virus-infested. “We want to understand why the infection progresses in some patients, so harmless, and why others become seriously ill. To do this we will look at the immune cells in the infected tissue more accurately,” says Eils. “The better we understand the interactions between the Virus and its host, the better we will be able to develop counter-strategies.”
source: Soeren Lukassen (Charité Universitätsmedizin Berlin) et al., EMBO Journal, doi: 10.15252/embj.20105114
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