“Hotspots” of SARS-CoV-2 infection in the human body

Infection with the coronavirus SARS-CoV-2 can affect multiple organs. With this in mind, researchers at the German Center for Neurodegenerative Diseases (DZNE) and Cornell University in the United States investigated cellular factors that could be important for infectious diseases. To this end, they analyzed the activity of 28 specific genes in a wide range of human tissues. Their findings, which provide a map of potential disease-related factors throughout the human body, are published in the journal Cell report..

“SARS-CoV-2 is Respiratory system, It can affect many other organs in the body. Even if the virus first infects the respiratory system, it is essential to be able to predict where it will go next. This helps in developing treatments. Dr. Vikas Bansal, data scientist at DZNE’s Tubingen site, explained: Therefore, which components of cellular tissue are associated with the infection Cell type Bansal co-authored his current paper with Manvendra Singh, Presidential Research Fellow at Cornell University, and co-authored with Cedric Feschotte, Professor of Molecular Biology and Genetics at Cornell University.

Search for candidates

Bansal began by working with colleagues in the United States to identify 28 human genes, respectively cellular factors, that allow the virus to enter humans. cell Or otherwise it may be important for the infection. In addition to cell surface receptors, these contained, for example, proteins that pathogens probably needed for intracellular growth. Importantly, the list of factors studied also includes enzymes known as “restrictor factors” that block the entry of pathogens into cells. In summary, the 28 cell functions analyzed are called “SCARF” in “SARS-CoV-2 and coronavirus-related receptors and factors.”

“This virus is known to abuse the so-called ACE2 receptor, which occurs on the surface of human cells, to dock and penetrate. Therefore, much attention is paid to this receptor and other factors associated with it. Has been paid. The point of treatment.” However, the coronaviruses involved are known to use a wide range of possibilities to infect cells. According to researchers, evidence suggests that this also applies to SARS-CoV-2. “Therefore, we expanded our analysis to cellular factors that may also be important for SARS-CoV-2 because they are known to be associated with other coronaviruses.”

Whether this is true or not, Bansal explained that future experiments need to show. About such an investigation, he said the purpose was to identify promising candidates. “But our research is just a snapshot. Research is evolving rapidly. We are constantly learning new facts about this virus.”

Gene activity profile

Using information from scientists’ databases, researchers analyzed gene activity (also called expression patterns) in approximately 400,000 human cells from various types of tissues. These included the nasal mucosa, lungs, intestines, kidneys, heart, brain and reproductive organs. The analysis was performed at the single cell level using sophisticated bioinformatics techniques. “This allowed us to investigate in which cells SCARF was expressed, and what percentage of cells within a particular tissue expressed these factors,” Bansal said. “Our results are certainly limited by the fact that expression patterns may change during the course of infection and such activity profiles do not directly reflect the amount of proteins such as cell receptors. The expression pattern is a good indicator.”

Battlefields and hotspots

In line with the known fact that SARS-CoV-2 specifically attacks the respiratory tract, the expression pattern identifies the nasal mucosa as a battlefield. Therefore, cells of the nasal mucosa contain both factors that promote infection, such as the ACE2 receptor, and factors that block viral entry, such as IFITM3 and LY6E. “IFITM3 is a protein known to prevent other coronaviruses from crossing the cell membrane. The same may apply to SARS-CoV-2. LY6E also acts as a defense mechanism.” Says Bansal. “Therefore, contact with the virus Nasal mucosa It leads to tug of war. So the question is who will be the winner. Interestingly, our data suggest that expression levels of entry factors in human nasal tissues change with age. This may be why older people are more susceptible to infection with SARS-CoV-2. “

According to current research, the intestines, kidneys, testes, and placenta are potential hotspots. Thus, these regions appear to be characterized by significant co-expression of TMPRSS2 and ACE2, the enzymes involved in viral entry with ACE2. “We could also identify many Cellular factor Bansal said that as an alternative to the ACE2 receptor, SARS-CoV-2 could contribute to its entry into the lungs, heart, and central nervous system. Although the virus has not yet been detected in neurons, the nervous system contains other cells, such as astrocytes and pericytes, which are involved in regulating the blood-brain barrier, which is the boundary between the brain and the bloodstream. It is According to our research, these cells infection.. This may involve a receptor called BSG. Therefore, overall, our research provides a wealth of data and specific clues for future research on coronaviruses. ”