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Título: | Severe acute respiratory syndrome coronaviruses with mutations in the E protein are attenuated and promising vaccine candidates |
Autor: | Regla-Nava, José Ángel ; Nieto-Torres, José L. ; Jiménez-Guardeño, José Manuel CSIC ORCID ; Fernandez-Delgado, Raúl ; Fett, Craig; Castaño-Rodríguez, Carlos ; Perlman, Stanley; Enjuanes Sánchez, Luis CSIC ORCID ; DeDiego, Marta L. CSIC ORCID | Fecha de publicación: | 1-abr-2015 | Editor: | American Society for Microbiology | Citación: | Journal of Virology 89(7): 3870-3887 (2015) | Resumen: | Severe acute respiratory syndrome coronavirus (SARS-CoV) causes a respiratory disease with a mortality rate of 10%. A mouseadapted 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-CoVMA15- 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. | Versión del editor: | http://dx.doi.org/10.1128/JVI.03566-14 | URI: | http://hdl.handle.net/10261/204163 | DOI: | 10.1128/JVI.03566-14 | Identificadores: | doi: 10.1128/JVI.03566-14 issn: 1098-5514 pmid: 25609816 |
Aparece en las colecciones: | (PTI Salud Global) Colección Especial COVID-19 (CNB) Artículos |
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