The ability of new coronavirus to break through the defense line of human body is really too strong!

A large-scale multinational team "checks" one by one in the vast database, finds three types of cells most likely to be directly attacked by the new coronavirus, and finds another cunning of its invasion of human cells. Sharing these data and findings as soon as possible will help focus on the role of the new coronavirus in the human body, "figuring out why some people are more susceptible to infection and how best to find a cure," the study authors said.

Cells that are vulnerable to invasion

Two months ago, the academic team of longitude and latitude reported the two key points needed by the new coronavirus to invade cells: the ACE2 receptor that the virus uses to bind, and the TMPRSS2 protease that helps the virus invade. However, it has not been clarified which cells express these two kinds of proteins. To find these cells, researchers from nearly 50 different institutions around the world, led by scientists from MIT and Boston Children's Hospital, have conducted large-scale screening work in the past two months to find the cells most likely to be infected with the new coronavirus.

The team used "single cell RNA sequencing technology" to answer this question, which can know which genes will be activated in each specific cell type. As long as one cell expresses both ACE2 and TMPRSS2, the risk of infection by the new coronavirus is very high.

The results showed that less than 10% of human respiratory and intestinal cells produced ACE2 and TMPRSS2 at the same time. These cells can be divided into 3 types: the first is goblet secretory cells in the nasal cavity, whose normal function is to secrete nasal mucus; the second is type II alveolar cells in the lung Pneumocytes), which is responsible for maintaining the function of the alveoli, while the third kind of cells is very interesting. It does not come from the respiratory tract, but from the digestive tract, which is called the absorptive intestinal epithelial cells. As the name suggests, it is located in the small intestine, responsible for the absorption of nutrients.

This finding is of great significance for all kinds of studies that need to carry out cell experiments to screen drugs. "Many existing respiratory cell lines may not contain all cell types (which will be infected by the new coronavirus), and relevant cells may be missed." Dr. Jose ordovas montanes, one of the leaders of this study, pointed out: "with more accurate cell models, we can be more targeted when screening drugs, providing a more solid foundation for subsequent experiments in mice and non-human primates."


▲ The results of macaque samples show that their susceptible cell pattern is similar to that of human

Interferon: good or bad?

Originally, this work has made great sense. But after identifying the types of cells that are susceptible to infection, scientists asked, how do these cells work?

This led the researchers to discover an unexpected phenomenon that may be of great significance in the treatment of new coronavirus disease - the gene encoding ACE2 increases expression in epithelial cells stimulated by interferon! Interferon is a kind of cytokines secreted by the human immune system after detecting the virus, which usually plays an important role in the defense of the virus. However, interferon up regulates ACE2, which means that there are more "Gates" on the cell surface for the new coronavirus to enter.


ACE2 plays an important protective role in various lung injuries "When ACE2 increases, it's usually a protective response," explains Dr. ordovas montanes. However, since the new coronavirus targets ACE2, we suspect that the normal protective response has been exploited by the new coronavirus. "

For example, in the clinical treatment of patients with new crown disease, doctors will also use interferon to fight against virus infection. But the discovery suggests that this treatment may instead allow patients to express more ACE2, making more cells likely to be infected by the new coronavirus. It is necessary to find a balance between the advantages and disadvantages of interferon use.

Scientists have also described to us the potential cunning side of the new coronavirus: when infected with the virus, our body's interferon response may drive the production of a large number of ACE2. In general, ACE2 has the function of protecting the lung. However, the presence of these proteins will be used by the new coronavirus as a springboard for them to invade more cells. This may explain why some patients get worse after using interferon.