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.
Project description:Human circular RNAs can function in competing endogenous RNA (ceRNA) network by sponging miRNA and regulating gene expression. Viruses are evolved to regulate noncoding RNAs such as miRNAs and circRNAs to facilitate their propagation and pathogenesis. Studies on how host ceRNAs upon human coronavirus infection were scarce, and the functions of circRNAs during the infection of Middle East respiratory syndrome coronavirus (MERS-CoV) has not been deeply revealed. Therefore, we conducted a whole transcriptional profile (RNA-seq) analysis to compare the expression of circRNAs, miRNAs and mRNAs between the mock-infected and MERS-CoV-infected human lung adenocarcinoma (Calu-3) cells. Integrated analysis of ceRNAs revealed putative viral pathogenic circRNAs induced by MERS-CoV and their interplay with miRNAs and genes. Our study offered new insights into the mechanisms of interplays of MERS-CoVs and hosts, and established a model promising to be applied to other coronavirus or other viruses for the identification of novel host factors.
Project description:An infection with SARS-CoV-2 can be symptomatic or asymptomatic depending on the respective activation of the immune system. We used the bacterial extract Broncho Vaxom (BV) to preactivate the immune system before a coronavirus infection using the murine coronavirus MHV A59 in a mouse model. The activation of the immune system led to a reduction in viral load and protected lung tissue from enhanced cell apoptosis. Using RNA sequencing we were able to demonstrate that lung tissue from mice receiving BV resembled an intermediate state between infected and healthy tissue. On a cellular level, treatment with BV enhanced alveolar and interstitial macrophages in the lung. We were able to phenocopy the effect of BV by transplanting naïve lung macrophages into recipient mice thereby enhancing the local cellular amount before infection. We conclude that recruitment and preactivation of the innate immune system by the bacterial extract BV is beneficial during a coronavirus infection.
Project description:LY6E is an antiviral restriction factor that inhibits coronavirus spike-mediated fusion, but the cell types in vivo that require LY6E for protection from respiratory coronavirus infection are unknown. Here, we used a panel of seven conditional Ly6e knockout mice to define which Ly6e-expressing cells confer control of airway infection by murine coronavirus and SARS-CoV-2. Loss of Ly6e in Lyz2-expressing cells, radioresistant Vav1-expressing cells, and non-hematopoietic cells increased susceptibility to murine coronavirus. Global conditional loss of Ly6e expression resulted in clinical disease and higher viral burden after SARS-CoV-2 infection, but little evidence of immunopathology. We show that Ly6e expression protected secretory club and ciliated cells from SARS-CoV-2 infection and prevented virus-induced loss of an epithelial cell transcriptomic signature in the lung. Our study demonstrates that lineage confined rather than broad expression of Ly6e sufficiently confers resistance to disease caused by murine and human coronaviruses.
Project description:Differential expression was determined in Calu-3 cells between mock infected and infection with either Human coronavirus EMC and SARS coronavirus at different times post infection. Calu-3 2B4 cells were infected with Human Coronavirus EMC 2012 (HCoV-EMC) or mock infected. Samples were collected 0, 3, 7, 12, 18 and 24 hpi. There are 3 mock and 3 infected replicates for each time point, except for 12 hpi for which there are only 2 infected replicates (one replicate did not pass RNA quality check). There were no mock sampes at 18 hpi, and therefore infected samples at 18 hpi were compared with mocks at 24 hpi. For direct comparison with SARS-CoV infected cells, raw data from HCoV-EMC experiments were quantile normalized together with the SARS-CoV dataset (GEO Series accession number GSE33267).
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:Tropism is a very important factor in pneumococcal infection. Previous study has shown that clinical isolate showed niche preference in model organism. In particular, ear isolate showed particular tropism in nasopharyngeal carriage while blood isolate survives better in the murine lung. We have detected a SNP located inside rafR, repressor of sugar metabolism regulon, that contributes to strain tropism. We then perform a swap mutation between the rafR ear and blood isolates and perform intranasal infection using the four strains: original ear and blood isolates, ear isolate with rafR blood isolate and blood isolate with rafR ear isolate. We harvested the lung six hours into infection and exploited the recently described dual RNA-seq to reconstruct transcriptomics landscape during host-pathogen interaction.
Project description:Gene expression of 770 genes from the Nanostring Neuroinflammation panel in the coronavirus-induced encephalomyelitus (CIE) murine model of multiple sclerosis.