A critical gene that causes death in patients infected with COVID-19 has been discovered. It is ‘ZBP1’, one of the innate immune sensors that recognize viral infection in cells.
Professor Lee Sang-jun from UNIST’s Department of Life Sciences (President Lee Yong-hoon) published a study that ‘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 Corona virus 19 (SARS-CoV-2) penetrates, it makes 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.
Professor Sang-Jun Lee’s team found the ZBP1 gene using genome-wide CRISPR-Cas9 screening, which removes genes from macrophages infected with Corona virus 19. Macrophages with this gene are killed by a cytokine storm following infection with Corona virus 19, but macrophages with this gene removed did not die even after infection with Corona virus 19.
According to this study, the ZBP1 gene is particularly aware of the COVID-19 virus 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, simultaneous inflammatory cell death (PANoptosis) occurs. This apoptosis causes systemic inflammation, or 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.”
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 conducted in collaboration with St. Jude Children’s Research Hospital in the United States, and the results of the study were published in ‘Science Immunology’ (Title of the paper: ZBP1-dependent inflammatory cell death, PANoptosis, and cytokine storm impair IFN efficacy therapeutic during coronavirus infection)