Generation of a lethal mouse model expressing human ACE2 and TMPRSS2 for SARS-CoV-2 infection and pathogenesis

초록

Mouse models expressing human ACE2 for coronavirus disease 2019 have been frequently used to understand its pathogenesis and develop therapeutic strategies against SARS-CoV-2. Given that human TMPRSS2 supports viral entry, replication, and pathogenesis, we established a double-transgenic mouse model expressing both human ACE2 and TMPRSS2 for SARS-CoV-2 infection. Co-overexpression of both genes increased viral infectivity in vitro and in vivo. Double-transgenic mice showed significant body weight loss, clinical disease symptoms, acute lung injury, lung inflammation, and lethality in response to viral infection, indicating that they were highly susceptible to SARS-CoV-2. Pretreatment with the TMPRSS2 inhibitor, nafamostat, effectively reduced virus-induced weight loss, viral replication, and mortality in the double-transgenic mice. Moreover, the susceptibility and differential pathogenesis of SARS-CoV-2 variants were demonstrated in this animal model. Together, our results demonstrate that double-transgenic mice could provide a highly susceptible mouse model for viral infection to understand SARS-CoV-2 pathogenesis and evaluate antiviral therapeutics against coronavirus disease 2019. This research aimed to create a type of mouse that is very prone to SARS-CoV-2 infection, the virus that causes COVID-19. Scientists from two Korean research institutes found that mice with both human angiotensin-converting enzyme 2 (hACE2, a protein that the virus uses to enter cells) and human transmembrane serine protease 2 (hTMPRSS2, an enzyme that helps the virus to infect cells) were very prone to the virus. They created mice with both these human genes, infected them with different amounts of SARS-CoV-2, and observed significant weight loss, disease symptoms, and death, similar to what happens in COVID-19 patients. The scientists concluded that these mice could help us understand how the virus infects and causes disease, and test potential treatments against COVID-19. The study could also help in developing future drugs and vaccines.This summary was initially drafted using artificial intelligence, then revised and fact-checked by the author.