JEM: Research and development of SARS-coV-2 mouse models.

March 20, 2020 /--- In a recent study published in the journal Journal of Experiments Medicine, researchers at Yale University School of Medicine developed a new mouse model to study SARS-CoV-2 infections and diseases and accelerate testing of new therapies and vaccines for new coronaviruses.
study also suggests that key antiviral signaling proteins can cause many tissue damage associated with COVID-19.
mice are the most widely used experimental animals, but they cannot be infected with SARS-CoV-2 because the virus does not recognize and bind to ACE2 in mice.
SARS-CoV-2 can infect mice genetically engineered to produce humanized ACE2.
, however, the animals are of low practicality and are limited to a single mouse line.
(Photo source: www.pixabay.com) In the new study, Professor Iwasaki's lab at Yale University School of Medicine developed another mouse model of SARS-CoV-2 infection, in which animals were first infected with another harmless virus carrying the human ACE2 gene.
mice infected with the virus produce the human ACE2 protein, which in turn can infect mice with SARS-CoV-2.
Iwasaki and colleagues found that SARS-CoV-2 could replicate and induce inflammatory reactions similar to those observed in COVID-19 patients, where multiple immune cells were activated and collected into the lungs.
, infected mice quickly developed a leveling antibody against SARS-CoV-2," said Iwasaki.
" response to viral infections usually depends on type I interferon, a signaling molecule that activates immune cells and induces the production of antiviral proteins and antibodies.
but too many type I interferons, especially when production is delayed, can lead to excessive inflammation and tissue damage.
although type I interferon signal transdulsion protects against the associated coronavirus MERS-CoV, it can cause lung damage in response to SARS-CoV-1.
is not clear about the role of type I interferon in COVID-19.
Iwasaki and colleagues found that, similar to COVID-19 patients, mice infected with SARS-CoV-2 activated a large number of genes associated with type I interferon signaling.
, the researchers then used their model system to infect mice lacking key components of the Type I interferon pathway and found that they were not bad at controlling SARS-CoV-2 infection.
, however, these animals collect fewer inflammatory immune cells from the lungs.
These results suggest that type I interferons do not limit the replication of SARS-CoV-2, but they may play a pathological role in COVID-19 respiratory inflammation," Iwasaki said.
is particularly worrying because type I interferon is currently being used as a treatment for COVID-19.
early ONN treatment is critical to its protection and benefits.
Iwasaki added: "The mouse model we developed provides a wide range of highly adaptable animal models available to understand the pathogenesis of SARS-CoV-2 virus infection, replication, and pathogenesis.
model provides an important platform for testing prevention and treatment strategies against COVID-19.
(bioon.com) Source: Researchers development new mouse model for SARS-CoV-2 Source: enjamin Israelow, Eric Song, Tianyang Mao, Peiwen Lu, Amit Meir, Feimei Liu, Mia Madel Alfajaro, Jin Wei, Huiping Dong, Robert J. Homer, Aaron Ring, B. Wilen, Akiko Iwasaki. Mouse model of SARS-CoV-2 reveals the role of type I interferon signaling. Journal of The International Medicine, 2020; 217 (12) DOI: 10.1084/jem.20201241.