Severe acute respiratory syndrome coronavirus envelope protein regulates cell stress response and apoptosis

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. © 2011 dediego et al.