RT Journal Article
T1 Severe acute respiratory syndrome coronaviruses with mutations in the E protein are attenuated and promising vaccine candidates
A1 Regla-Nava, Jose Angel
A1 Nieto-Torres, Jose Luis
A1 Jimenez-Guardeño, Jose Manuel
A1 Fernandez-Delgado, Raul
A1 Fett, Craig
A1 Castaño-Rodriguez, Carlos
A1 Perlman, Stanley
A1 Enjuanes, Luis
A1 DeDiego, Marta L.
K1 Virus
AB 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.
PB ASM Journals
YR 2015
FD 2015
LK https://hdl.handle.net/10630/37371
UL https://hdl.handle.net/10630/37371
LA eng
NO Regla-Nava JA, Nieto-Torres JL, Jimenez-Guardeño JM, Fernandez-Delgado R, Fett C, Castaño-Rodríguez C, Perlman S, Enjuanes L, DeDiego ML 2015. Severe Acute Respiratory Syndrome Coronaviruses with Mutations in the E Protein Are Attenuated and Promising Vaccine Candidates. J Virol 89:. https://doi.org/10.1128/jvi.03566-14
DS RIUMA. Repositorio Institucional de la Universidad de Málaga
RD 19 ene 2026