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Multi-omics evaluation of SARS-CoV-2 infected mouse lungs reveals dynamics of host responses.

ABSTRACT: The outbreak of Coronavirus disease 2019 (COVID-19) throughout the world has caused millions of death, while the dynamics of host responses and the underlying regulation mechanisms during SARS-CoV-2 infection are not well depicted. Lung tissues from a mouse model sensitized to SARS-CoV-2 infection were serially collected at different time points for evaluation of transcriptome, proteome, and phosphoproteome. We showed the ebb and flow of several host responses in the lung across the viral infection. The signaling pathways and kinases regulating networks were alternated at different phases of infection. This multiplex evaluation also revealed that many kinases of the CDK and MAPK family were interactive and served as functional hubs in mediating the signal transduction during SARS-CoV-2 infection. Our study not only revealed the dynamics of lung pathophysiology and their underlying molecular mechanisms during SARS-CoV-2 infection, but also highlighted some molecules and signaling pathways that might guide future investigations on COVID-19 therapies.

SUBMITTER: Wang ZN

PROVIDER: S-EPMC8863311 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Multi-omics evaluation of SARS-CoV-2 infected mouse lungs reveals dynamics of host responses

Project description:Lung tissues from a mouse model sensitized to SARS-CoV-2 infection were serially collected at different time points for evaluation of transcriptome, proteome and phosphoproteome. We showed the ebb and flow of several host responses in the lung across viral infection. The signaling pathways and kinases regulating networks were alternated at different phases of infection. Our study not only revealed the dynamics of lung pathophysiology and their underlying molecular mechanisms during SARS-CoV-2 infection, but also highlighted some molecules and signaling pathways that might guide future investigations on COVID-19 therapies.

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Multi-omics evaluation of SARS-CoV-2 infected mouse lungs reveals dynamics of host responses

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Absence of host innate immune responses in SARS-CoV-infected ferrets upon subsequent challenge

Project description:To further investigate the underlying mechanisms of severe acute respiratory syndrome (SARS) pathogenesis and evaluate the therapeutic efficacy of potential drugs and vaccines it is necessary to use an animal model that is highly representative of the human condition in terms of respiratory anatomy, physiology and clinical sequelae. The ferret, Mustela putorius furo, supports SARS-CoV replication and displays many of the symptoms and pathological features seen in SARS-CoV-infected humans. We have recently established a SARS-CoV infection-challenge ferret platform for use in evaluating potential therapeutics to treat SARS. The main objective of the current study was to extend our previous results and identify early host immune responses upon infection and determine immune correlates of protection upon challenge with SARS-CoV in ferrets. Keywords: time course This study is a simple time course (58 day) examination of host responses in 35 SARS-CoV (TOR2) infected ferrets with the addition of a challenge inoculation of SARS CoV (TOR2) at day 29 post infection. Three mock-infected ferrets are included as negative controls. Due to the unavailability of ferret microarrays, Affymetrix Canine 2.0 oligonucleotide arrays were chosen following sequence analysis of our ferret cDNA library (~5000 clones) and demonstration of high levels of homology (>80%) between dog and ferret.

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