Journal article
Severe acute respiratory syndrome coronavirus envelope protein regulates cell stress response and apoptosis
PLoS pathogens, Vol.7(10), e1002315
10/2011
DOI: 10.1371/journal.ppat.1002315
PMCID: PMC3197621
PMID: 22028656
Abstract
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.
Details
- Title: Subtitle
- Severe acute respiratory syndrome coronavirus envelope protein regulates cell stress response and apoptosis
- Creators
- Marta L DeDiego - Department of Molecular and Cell Biology, Centro Nacional de Biotecnología (CNB-CSIC), Campus Universidad Autónoma de Madrid, Madrid, SpainJose L Nieto-TorresJose M Jiménez-GuardeñoJose A Regla-NavaEnrique AlvarezJuan Carlos OliverosJincun ZhaoCraig FettStanley PerlmanLuis Enjuanes
- Resource Type
- Journal article
- Publication Details
- PLoS pathogens, Vol.7(10), e1002315
- DOI
- 10.1371/journal.ppat.1002315
- PMID
- 22028656
- PMCID
- PMC3197621
- NLM abbreviation
- PLoS Pathog
- ISSN
- 1553-7366
- eISSN
- 1553-7374
- Publisher
- United States
- Grant note
- R56 AI079424 / NIAID NIH HHS\r\nR56 AI079424-01A1 / NIAID NIH HHS\r\nP01 AI060699 / NIAID NIH HHS\r\n2P01 AI060699 / NIAID NIH HHS
- Language
- English
- Date published
- 10/2011
- Academic Unit
- Microbiology and Immunology; Stead Family Department of Pediatrics; Iowa Neuroscience Institute; Infectious Disease (Pediatrics)
- Record Identifier
- 9983777474302771
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