TY - JOUR T1 - Severe Acute Respiratory Syndrome Coronavirus Envelope Protein Regulates Cell Stress Response and Apoptosis A1 - DeDiego, Marta L. A1 - Nieto-Torres, Jose L. A1 - Jiménez-Guardeño, Jose M. A1 - Regla-Nava, Jose A. A1 - Álvarez, Enrique A1 - Oliveros, Juan Carlos A1 - Zhao, Jincun A1 - Fett, Craig A1 - Perlman, Stanley A1 - Enjuanes, Luis Y1 - 2011/10/20 N2 - Author Summary To identify potential mechanisms mediating the in vivo attenuation of SARS-CoV lacking the E gene (rSARS-CoV-ΔE), the effect of the presence of the E gene on host gene expression was studied. In rSARS-CoV-ΔE-infected cells, the expression of at least 25 stress response genes was preferentially upregulated, compared to cells infected with rSARS-CoV. E protein supplied in trans reversed the increase in stress response genes observed in cells infected with rSARS-CoV-ΔE or with respiratory syncytial virus, and by treatment with drugs causing stress by different mechanisms. Furthermore, in the presence of the E protein a subset (IRE-1 pathway), but not two others (PERK and ATF-6), of the unfolded protein response was also reduced. Nevertheless, the activation of the unfolded protein response to control cell homeostasis was not sufficient to alleviate cell stress, and an increase in cell apoptosis in cells infected with the virus lacking E protein was observed. This apoptotic response was probably induced to protect the host by limiting virus production and dissemination. In cells infected with rSARS-CoV-ΔE, genes associated with the proinflammatory pathway were down-regulated compared to cells infected with virus expressing E protein, supporting the idea that a reduction in inflammation was also relevant in the attenuation of the virus deletion mutant. JF - PLOS Pathogens JA - PLOS Pathogens VL - 7 IS - 10 UR - https://doi.org/10.1371/journal.ppat.1002315 SP - e1002315 EP - PB - Public Library of Science M3 - doi:10.1371/journal.ppat.1002315 ER -