Project description:Purpose of experiment was to perform transcriptomic analysis on C57Bl/6 mice infected with different doses of SARS CoV MA15 at 4 different days post infection.
Project description:Purpose of experiment was to perform transcriptomic analysis on C57Bl/6 mice infected with different doses of SARS CoV MA15 at 4 different days post infection. Twenty-week-old C57BL/6 mice were infected by intranasal instillation of 10^2, 10^3, 10^4 or 10^5 PFU of SARS CoV MA15 in 50 µl of PBS or mock-infected with PBS alone. At days 1, 2, 4 and 7 days post-infection, lungs were harvested and total RNA was isolated and subjected to microarray analysis. The experimental design was for 4- 5 mice/time point/dose and 3 time-matched mocks. The NIAID Systems Virology Center
Project description:Severe acute respiratory syndrome coronavirus (SARS-CoV) causes a respiratory disease leading to death in 10% of the infected people. A mouse adapted SARS-CoV lacking the envelope (E) protein (rSARS-CoV-MA15-?E) is attenuated in vivo. To identify E protein domains and host responses that contribute to rSARS-CoV-MA15-?E attenuation, several mutants (rSARS-CoV-MA15-E*) containing point mutations or deletions in the amino-terminal or the carboxy-terminal regions of E protein, respectively, were generated. Amino acid substitutions in the amino terminus, or deletion of domains in the internal carboxy terminal region of E protein led to viral attenuation. Attenuated viruses induced minimal lung injury and limited neutrophil influx to the lungs but, interestingly, increased CD4+ and CD8+ T cell counts in BALB/c mice. To analyze the host responses leading to rSARS-CoV-MA15-E* attenuation, the differential gene expression elicited by the native virus and the mutant ones in infected cells was analyzed. The expression levels of a large number of proinflammatory cytokines inducing lung injury was reduced in the lungs of rSARS-CoV-MA15-E* infected mice, whereas the levels of anti-inflammatory cytokines were increased, both at the mRNA and protein levels. These results suggested that the reduction in lung inflammation together with a specific antiviral T cell response, contributed to rSARS-CoV-MA15-E* attenuation. Interestingly, the attenuated viruses completely protected mice against the challenge with the lethal parental virus, being promising vaccine candidates. Three biological replicates were independently hybridized (one channel per slide) for each sample type (rSARS-CoV-MA15-wt, rSARS-CoV-MA15-?E, rSARS-CoV-MA15-?3, rSARS-CoV-MA15-?5, Mock). Slides were Sure Print G3 Agilent 8x60K Mouse (G4852A-028005)
Project description:Lung samples were generated from male mice of C57BL/6J(B6), C57BL/6JHamSlc-ob/ob (ob/ob) and C57BLKS/J-db/db on 3 days post infection of mouse-adapted SARS-CoV-2
Project description:Here, we systemically profile transcriptional responses to SARS-CoV-2 and IAV in the Syrian golden hamster infection model at 3 and 31 days post-infection. In doing this, we are able to benchmark SARS-CoV-2-induced host-responses against those induced by IAV and highlight unique pathologies that occur in response to SARS-CoV-2 at the peak of infection and following viral clearance. Through profiling of neural (olfactory bulb, medial prefrontal cortex, thalamus, striatum, cerebellum, trigeminal ganglion) and peripheral organ (lung, heart, kidney) tissues, we are able to show that while both viruses are able to induce systemic IFN-I responses and immune activation during acute infection, SARS-CoV-2 induces a uniquely localized and persistent inflammatory phenotype in the olfactory bulb that persists out to 31 days post-infection.
Project description:The purpose is to determine the role of TLR3-/- on the regulation of the host immune response during lethal SARS-CoV infection Groups of 10 week old C57BL6/NJ or TLR3-/- mice were infected with MA15 virus at a dose of 10^5 PFU or time-matched mock infected. Time points were 2, 4 and 7 days post infection. There were 4 or 5 animals/time point. Lung samples were collected for virus load, lung pathology, and transcriptional analysis. Weight loss and animal survival were also monitored.
Project description:Lung samples were generated from male mice of C57BL/6JHamSlc-ob/ob (ob/ob) and C57BLKS/J-db/db on 3 days post infection of mouse-adapted SARS-CoV-2 or non-infected condition
Project description:To dissect the nature of the immune dysregulation induced by SARS-CoV-2 infection in mouse lungs using mouse-adapted strains of the virus. Comparisons were performed using bulk RNA-seq data from mouse (C57BL/6) lung homogenates taken 3 days post-infection with mouse-adapted SARS-CoV-2, both early and late (virulent) passages, or mock-infected mice.
Project description:Lean or obese C57BL/6JHamSlc-ob/ob (ob/ob) were developed continuous leptin (or vehicle) treatment for 6 weeks. Lung samples were generated from male mice of lean or obese ob/ob on 3 days post infection of mouse-adapted SARS-CoV-2.
