SARS-CoV-2 has caused a global pandemic of COVID-19 since its emergence in December 2019. The infection causes a severe acute respiratory syndrome and may also spread to central nervous system leading to neurological sequelae. We have developed and characterized two new organotypic cultures from hamster brainstem and lung tissues that offer a unique opportunity to study the early steps of viral infection and screening antivirals. These models are not dedicated to investigate how the virus reaches the brain. However, they allow validating the early tropism of the virus in the lungs and demonstrating that SARS-CoV-2 could infect the brainstem and the cerebellum, mainly by targeting granular neurons. Viral infection induces specific interferon and innate immune responses with patterns specific to each organ, along with cell death by apoptosis, necroptosis, and pyroptosis. Overall, our data illustrate the potential of rapid modeling of complex tissue-level interactions during infection by a newly emerged virus. Here, Ferren et al. isolate Syrian hamster brainstem and lung tissue to establish ex vivo culture systems to study SARS-CoV-2 local viral tropism, immune response and tissue pathology. Further, they provide evidence that these systems can be used for screening of anti-viral compounds.
【저자키워드】 SARS-CoV-2, viral pathogenesis, 【초록키워드】 COVID-19, Apoptosis, viral infection, immune response, innate immune response, antivirals, Infection, interferon, lung, Local, virus, Brain, Anti-viral, global pandemic, Culture, pyroptosis, Central nervous system, cell death, compounds, neurons, Evidence, Interaction, neurological, necroptosis, viral tropism, Ex vivo, acute respiratory syndrome, complex, lung tissue, organ, offer, infect, tissue pathology, caused, spread to, granular, characterized, can be used, unique, induce, cause, 【제목키워드】 Infection, lung, hamster,