Inhibition of NF-κB-mediated inflammation in severe acute respiratory syndrome coronavirus-infected mice increases survival

Marta L DeDiego; Jose L Nieto-Torres; Jose A Regla-Nava; Jose M Jimenez-Guardeño; Raul Fernandez-Delgado; Craig Fett; Carlos Castaño-Rodriguez; Stanley Perlman; Luis Enjuanes

doi:10.1128/JVI.02576-13

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Inhibition of NF-κB-mediated inflammation in severe acute respiratory syndrome coronavirus-infected mice increases survival

Journal article

Open access

Peer reviewed

Inhibition of NF-κB-mediated inflammation in severe acute respiratory syndrome coronavirus-infected mice increases survival

Marta L DeDiego, Jose L Nieto-Torres, Jose A Regla-Nava, Jose M Jimenez-Guardeño, Raul Fernandez-Delgado, Craig Fett, Carlos Castaño-Rodriguez, Stanley Perlman and Luis Enjuanes

Journal of virology, Vol.88(2), pp.913-924

01/2014

DOI: 10.1128/JVI.02576-13

PMCID: PMC3911641

PMID: 24198408

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https://europepmc.org/articles/pmc3911641View

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Abstract

Severe acute respiratory syndrome coronavirus (SARS-CoV) is the etiological agent of a respiratory disease that has a 10% mortality rate. We previously showed that SARS-CoV lacking the E gene (SARS-CoV-ΔE) is attenuated in several animal model systems. Here, we show that absence of the E protein resulted in reduced expression of proinflammatory cytokines, decreased numbers of neutrophils in lung infiltrates, diminished lung pathology, and increased mouse survival, suggesting that lung inflammation contributed to SARS-CoV virulence. Further, infection with SARS-CoV-ΔE resulted in decreased activation of NF-κB compared to levels for the wild-type virus. Most important, treatment with drugs that inhibited NF-κB activation led to a reduction in inflammation and lung pathology in both SARS-CoV-infected cultured cells and mice and significantly increased mouse survival after SARS-CoV infection. These data indicated that activation of the NF-κB signaling pathway represents a major contribution to the inflammation induced after SARS-CoV infection and that NF-κB inhibitors are promising antivirals in infections caused by SARS-CoV and potentially other pathogenic human coronaviruses.

Viral Envelope Proteins - genetics

Severe Acute Respiratory Syndrome - virology

Down-Regulation

Humans

NF-kappa B - immunology

Severe Acute Respiratory Syndrome - immunology

Severe Acute Respiratory Syndrome - mortality

Animals

SARS Virus - genetics

NF-kappa B - genetics

Viral Envelope Proteins - metabolism

Severe Acute Respiratory Syndrome - genetics

Female

Mice

Mice, Inbred BALB C

SARS Virus - physiology

Cytokines - genetics

Cytokines - immunology

Details

Title: Subtitle: Inhibition of NF-κB-mediated inflammation in severe acute respiratory syndrome coronavirus-infected mice increases survival
Creators: Marta L DeDiego - Department of Molecular and Cell Biology, National Center of Biotechnology, Campus Universidad Autónoma de Madrid, Madrid, Spain
Jose L Nieto-Torres
Jose A Regla-Nava
Jose M Jimenez-Guardeño
Raul Fernandez-Delgado
Craig Fett
Carlos Castaño-Rodriguez
Stanley Perlman
Luis Enjuanes
Resource Type: Journal article
Publication Details: Journal of virology, Vol.88(2), pp.913-924
DOI: 10.1128/JVI.02576-13
PMID: 24198408
PMCID: PMC3911641
NLM abbreviation: J Virol
ISSN: 0022-538X
eISSN: 1098-5514
Publisher: United States
Grant note: HHSN266200700010C / PHS HHS 2P01AI060699-06A1 / NIAID NIH HHS HHSN266200700010C / NIAID NIH HHS P01 AI060699 / NIAID NIH HHS
Language: English
Date published: 01/2014
Academic Unit: Microbiology and Immunology; Stead Family Department of Pediatrics; Iowa Neuroscience Institute; Infectious Disease (Pediatrics)
Record Identifier: 9983777354602771

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