Project description:Canine parvovirus (CPV) infection poses a serious threat to pangolins, but the characteristics of the host response at the metabolic level remain unclear. In this study, we used non-targeted fecal metabolomics to systematically analyze differences in fecal metabolites in the Malaysian pangolin and the Chinese pangolin before and after CPV infection. The results indicated that CPV infection significantly altered the fecal metabolic profiles of both pangolin species. In the Malaysian pangolin, post-infection differential metabolites were primarily enriched in lipid metabolic pathways, such as α-linolenic acid and arachidonic acid metabolism, as well as inflammation-related pathways, including ferroptosis and necrotic apoptosis. Whereas the Chinese pangolin exhibited not only lipid metabolism dysregulation but also amino acid metabolic reprogramming and bile acid metabolism dysregulation. There were significant differences in metabolic responses between the two species, with the Malaysian pangolin characterized by lipid metabolism abnormalities, while the Chinese pangolin showed a greater focus on amino acid and bile acid metabolism. This study revealed the specific metabolic response of pangolins infected with CPV, provided potential fecal metabolic biomarkers for the early identification of CPV infection in pangolins, and provided a new theoretical basis for disease monitoring and intervention in pangolin conservation medicine.
Project description:The natural host of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remains elusive. A panel of SARS-CoV-2-related coronaviruses have been identified in pangolins, while the infectivity and pathogenicity of these pangolin-origin coronaviruses (pCoV) to human remains largely unknown. Herein, we comprehensively characterized the infectivity and pathogenicity of pCoV-GD01, the most closest pCoV to SARS-CoV-2, in human cells, human tracheal epithelium organoids, and established animal models in comparision with. The results show that pCoV-GD01 showed similar infectivity to SARS-CoV-2 in human cells and organoids. Remarkably, intranasal inoculation of pCoV-GD01 caused severe lung pathological damage in hACE2 mice, and could establish efficient transmission among co-caged hamsters. Interestingly, in-depth antigenic analysis and animal heterologous challenge experiments demonstrate that pre-existing immunity induced by SARS-CoV-2 infection or vaccination was sufficient to provide cross-protection against pCoV-GD01 challenge. These collective results highlight the potential risk of persistent spillover from animal hosts like the pangolin, and the COVID-19 pandemic and massive vaccination have reduced the possibility of pCoVs circulation in mankind.
Project description:Set of microarray experiments used to identify an unknown coronavirus in a viral culture derived from a patient with SARS. March 2003. Keywords = SARS Keywords = coronavirus Keywords = viral discovery Keywords = viruses Keywords = respiratory infection
Project description:Impaired type I interferon (IFN) responses are predictive of severe disease during pulmonary coronavirus infection. Insufficient IFN-responsiveness is associated with viremia and hypercytokinemia, however the resolution of IFN-dependent innate immune responses in the lungs remains limited. Here, we aimed to elucidate the early dynamics of antiviral immunity and define the IFN-dependent mechanisms limiting viral spread during pulmonary infection with the murine coronavirus A59 (M-CoV-A59), a beta-coronavirus. Combining high-resolution transcriptomic analysis and genetic attenuation of interferon signaling, we delineated IFN-dependent cell-intrinsic and population-based transcriptional changes that determined viral replication and inflammatory maturation, respectively.