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oai:riuma.uma.es:10630/332862026-02-03T11:16:09Zcom_10630_2254col_10630_37953

Severe acute respiratory syndrome coronavirus envelope protein regulates cell stress response and apoptosis. DeDiego, Marta L. Nieto-Torres, José Luis Jiménez-Guardeño, José Manuel Regla-Nava, Jose Ángel Álvarez, Enrique Oliveros, Juan Carlos Zhao, Jincun Fett, Craig Perlman, Stanley Enjuanes, Luis Síndrome respiratorio agudo grave COVID-19 - Influencia y consecuencias Severe acute respiratory syndrome virus (SARS-CoV) that lacks the envelope (E) gene (rSARS-CoV-ΔE) is attenuated in vivo. To identify factors that contribute to rSARS-CoV-ΔE attenuation, gene expression in cells infected by SARS-CoV with or without E gene was compared. Twenty-five stress response genes were preferentially upregulated during infection in the absence of the E gene. In addition, genes involved in signal transduction, transcription, cell metabolism, immunoregulation, inflammation, apoptosis and cell cycle and differentiation were differentially regulated in cells infected with rSARS-CoV with or without the E gene. Administration of E protein in trans reduced the stress response in cells infected with rSARS-CoV-ΔE or with respiratory syncytial virus, or treated with drugs, such as tunicamycin and thapsigargin that elicit cell stress by different mechanisms. In addition, SARS-CoV E protein down-regulated the signaling pathway inositol-requiring enzyme 1 (IRE-1) of the unfolded protein response, but not the PKR-like ER kinase (PERK) or activating transcription factor 6 (ATF-6) pathways, and reduced cell apoptosis. Overall, the activation of the IRE-1 pathway was not able to restore cell homeostasis, and apoptosis was induced probably as a measure to protect the host by limiting virus production and dissemination. The expression of proinflammatory cytokines was reduced in rSARS-CoV-ΔE-infected cells compared to rSARS-CoV-infected cells, suggesting that the increase in stress responses and the reduction of inflammation in the absence of the E gene contributed to the attenuation of rSARS-CoV-ΔE. 2024-09-25T15:38:58Z 2024-09-25T15:38:58Z 2011 journal article https://hdl.handle.net/10630/33286 10.1371/journal.ppat.1002315 eng http://creativecommons.org/licenses/by/4.0/ open access Attribution 4.0 Internacional PLOS