Journal Article

Hamster organotypic modeling of SARS-CoV-2 lung and brainstem infection

Weickert, Jean-Luc, Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC) ; Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Immunobiologie des infections virales – Immunobiology of Viral Infections [CIRI] (CIRI-IbIV) ; Centre International de Recherche en Infectiologie (CIRI) ; École normale supérieure de Lyon (ENS de Lyon) ; Université de Lyon-Université de Lyon-Université Claude Bernard Lyon 1 (UCBL) ; Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon) ; Université de Lyon-Université de Lyon-Université Claude Bernard Lyon 1 (UCBL) ; Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherc

2021

Overview

Abstract 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.

• Publisher: Nature Publishing Group,CCSD,Nature Publishing Group UK,Nature Portfolio
• Subject: 101/28 / 13 / 13/21 / 13/51 / 14/19 / 38/88 / 38/91 / 59 / 631/326/596/2555 / 631/326/596/4130 / 64 / Adenosine Monophosphate - analogs & derivatives / Adenosine Monophosphate - pharmacology / Alanine - analogs & derivatives / Alanine - pharmacology / Alveolar Epithelial Cells - virology / Animals / Antiviral agents / Antiviral Agents - pharmacology / Antiviral drugs / Apoptosis / Biotechnology / Brain stem / Brain Stem - cytology / Brain Stem - immunology / Brain Stem - pathology / Brain Stem - virology / Cell culture / Cell death / Cellular Biology / Central nervous system / Cerebellum / COVID-19 / Cricetinae / Emerging diseases / Human health and pathology / Humanities and Social Sciences / Immune response / Immune system / Immunity, Innate / Immunology / Infections / Inflammation / Innate immunity / Interferon / Life Sciences / Lung - cytology / Lung - immunology / Lung - pathology / Lung - virology / Lungs / Microbiology and Parasitology / Modelling / Models, Biological / multidisciplinary / Necroptosis / Neurological complications / Neurons - virology / Neurons and Cognition / Organ Culture Techniques / Pandemics / Pyroptosis / Regulated Cell Death / Respiratory diseases / SARS-CoV-2 - drug effects / SARS-CoV-2 - pathogenicity / Science / Science (multidisciplinary) / Screening / Severe acute respiratory syndrome coronavirus 2 / Subcellular Processes / Tropism / Viral diseases / Viral infections / Viral Tropism / Virology / Viruses