DESCRIPTION:

The GEO2R tool was used to analyze microarray data from mice either mock-infected or infected with SARS-CoV1. The Gene sets used in the analysis were from GSE59185. GEO2R was used with default parameters. Genes with an adjusted p-value of <0.05 and a log fold change <-1.0 are included in this set. EntrezGene identifiers or sequence identifiers were converted to MGI identifiers. Genes that could not be converted were omitted. If a gene was represented more than once, the largest fold-change was chosen.

LABEL:

down SARS-CoV1, lung

SCORE TYPE:

Binary

DATE ADDED:

2021-04-02

DATE UPDATED:

2024-04-25

SPECIES:

AUTHORS:

Jose A Regla-Nava, Jose L Nieto-Torres, Jose M Jimenez-Guardeño, Raul Fernandez-Delgado, Craig Fett, Carlos Castaño-Rodríguez, Stanley Perlman, Luis Enjuanes, Marta L DeDiego

TITLE:

Severe acute respiratory syndrome coronaviruses with mutations in the E protein are attenuated and promising vaccine candidates.

JOURNAL:

Journal of virology Apr 2015, Vol 89, pp. 3870-87

ABSTRACT:

Severe acute respiratory syndrome coronavirus (SARS-CoV) causes a respiratory disease with a mortality rate of 10%. A mouse-adapted SARS-CoV (SARS-CoV-MA15) lacking the envelope (E) protein (rSARS-CoV-MA15-ΔE) is attenuated in vivo. To identify E protein regions and host responses that contribute to rSARS-CoV-MA15-ΔE attenuation, several mutants (rSARS-CoV-MA15-E*) containing point mutations or deletions in the amino-terminal or the carboxy-terminal regions of the E protein were generated. Amino acid substitutions in the amino terminus, or deletion of regions in the internal carboxy-terminal region of E protein, led to virus attenuation. Attenuated viruses induced minimal lung injury, diminished limited neutrophil influx, and increased CD4(+) and CD8(+) T cell counts in the lungs of BALB/c mice, compared to mice infected with the wild-type virus. To analyze the host responses leading to rSARS-CoV-MA15-E* attenuation, differences in gene expression elicited by the native and mutant viruses in the lungs of infected mice were determined. Expression levels of a large number of proinflammatory cytokines associated with lung injury were 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 more robust antiviral T cell response contributed to rSARS-CoV-MA15-E* attenuation. The attenuated viruses completely protected mice against challenge with the lethal parental virus, indicating that these viruses are promising vaccine candidates. PUBMED: 25609816
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