“Why is the death rate from COVID-19 so high?” First discovery of a ‘gene’ that causes an excessive immune response. ” – The Herald Economics

– Professor Sang-Jun Lee from UNIST proves that it causes a cytokine storm after infection with COVID-19


[헤럴드경제=구본혁 기자] A critical gene that causes the death of patients infected with COVID-19 has been discovered by a Korean research team. It is ‘ZBP1’, one of the innate immune sensors ​​that recognize viral infection in cells.

Professor Sang-Jun Lee from the Department of Life Sciences of the Ulsan Institute of Science and Technology (UNIST) published a study showing that the ZBP1 gene, known as an innate immune sensor, increases the death rate of COVID-19 patients. This gene recognizes the virus that has penetrated the cell and gives a signal to make a cytokine, an immune protein. However, if the COVID-19 virus has penetrated, they make too many cytokines. This wind causes inflammation in the body due to an excessive immune response, leading to death.

Professor Lee Sang-jun said, “Immune cells play an important role in fighting pathogens, but if they are wrong, they are a ‘double-edged sword’ that attacks themselves, so there is a balance immune cell function is important. to cause death,” he said.

The research team found the ZBP1 gene using gene editing technology that removes the gene from macrophages infected with Corona virus 19. Macrophages with this gene are killed by a cytokine storm in following infection with Corona virus 19, but macrophages with this gene removed did not die even after infection with Corona virus 19.

According to research, the ZBP1 gene is particularly aware of the corona virus 19 that has penetrated into cells. It is good to detect danger signs well, but the problem is that more cytokines are produced than necessary. This is because, when too many cytokines are present, inflammatory cells die at the same time. This cell death causes systemic inflammation, a cytokine storm, which increases patient mortality.

The research team also found the reason why ‘Interferon (IFN) therapy’, commonly used to treat viruses, does not work well for COVID-19 patients. Interferon potently expresses the ZBP1 gene, which causes inflammatory cell death and a cytokine storm.

Professor Lee said, “Interferon is an immune substance that is secreted after the immune sensor recognizes a virus, etc., and it does not fight the virus itself, but acts as a messenger to create a protein that can fight it.” “The ZBP1 gene is also “It is believed to cause a cytokine storm when it is more strongly expressed.”

Sang-Jun Lee, Professor at UNIST.[UNIST 제공]

The relationship between the interferon and ZBP1 genes was also shown in experiments on small animals infected with the COVID-19 virus. All pups died only when interferon was injected while the ZBP1 gene was present. Not all small animals died when given either condition.

Professor Lee said, “If we can control the expression of the ZBP1 gene, we can create a new drug to treat COVID-19 patients by balancing the activation of immune cells. Because it is a preventive measure, it will be able to have universality that can treat any virus infection.”

This study was carried out in collaboration with the Children’s Research Hospital St. Jude in the United States, and the results of the study were published in the international scientific journal ‘Science Immunology’.


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