Project description:The severe acute respiratory syndrome (SARS) epidemic was characterized by increased pathogenicity in the elderly due to an early exacerbated innate host response. SARS-CoV is a zoonotic pathogen that entered the human population through an intermediate host like the palm civet. To prevent future introductions of zoonotic SARS-CoV strains and subsequent transmission into the human population, heterologous disease models are needed to test the efficacy of vaccines and therapeutics against both late human and zoonotic isolates. Here we show that both human and zoonotic SARS-CoV strains can infect cynomolgus macaques and resulted in radiological as well as histopathological changes similar to those seen in mild human cases. Viral replication was higher in animals infected with a late human phase isolate compared to a zoonotic isolate. Host responses to the three SARS-CoV strains were similar and only apparent early during infection with the majority of genes associated with interferon signalling pathways.This study characterizes critical disease models in the evaluation and licensure of therapeutic strategies against SARS-CoV for human use 4 strains, time course, lungs
Project description:The severe acute respiratory syndrome (SARS) epidemic was characterized by increased pathogenicity in the elderly due to an early exacerbated innate host response. SARS-CoV is a zoonotic pathogen that entered the human population through an intermediate host like the palm civet. To prevent future introductions of zoonotic SARS-CoV strains and subsequent transmission into the human population, heterologous disease models are needed to test the efficacy of vaccines and therapeutics against both late human and zoonotic isolates. Here we show that both human and zoonotic SARS-CoV strains can infect cynomolgus macaques and resulted in radiological as well as histopathological changes similar to those seen in mild human cases. Viral replication was higher in animals infected with a late human phase isolate compared to a zoonotic isolate. Host responses to the three SARS-CoV strains were similar and only apparent early during infection with the majority of genes associated with interferon signalling pathways.This study characterizes critical disease models in the evaluation and licensure of therapeutic strategies against SARS-CoV for human use
Project description:This study provides single-cell transcriptomic datasets from the lung and mediastinal lymph node tissues of cynomolgus macaques following primary or secondary infection with the SARS-CoV-2 Omicron variant. The dataset captures
Project description:Vascular disruption caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) leads to elevated levels of circulating endothelial cells (CECs); however, the role of CECs in SARS-CoV-2 remains uncharacterized. Here, we analyzed transcriptional changes in CECs from SARS-CoV-2-infected cynomolgus macaques that could reflect the pathophysiology of patients with coronavirus disease 2019 (COVID-19). We found that genes involved in metabolic processes and dysregulated immune responses were upregulated in CECs upon infection with SARS-CoV-2 compared with uninfected controls. Notably, immunization with a recombinant SARS-CoV-2 spike glycoprotein (GBP 510) stimulates CEC-induced protective immunity, marked by enhanced T cell proliferation and reduced neutrophil migration, both of which have been shown to contribute to the pathogenesis of severe COVID-19. These data provide insight into the clinical significance of CECs and suggest a potential novel therapeutic strategy for COVID-19.
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.
Project description:In this study, we established the COVID-19 infection model in cynomolgus macaques (CMs), the differentially expressed proteins was analyzed in lung tissue collected from 3 untreated (NC1-3) and 4 CMs inoculated with SARS-CoV-2 for 7 days (nCoV1-4). The results showed the differentially expressed genes (DEGs) before and after exposure. The median CV values was analyzed to confirm the proteomics data with good degree of consistency and reproducibility (median<0.25). The histogram of GO terms enriched in biological process, cellular component and molecular function.