Journal
JOURNAL OF VIROLOGY
Volume 88, Issue 2, Pages 913-924Publisher
AMER SOC MICROBIOLOGY
DOI: 10.1128/JVI.02576-13
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Funding
- Ministry of Science and Innovation of Spain [BIO2010-16705]
- European Commission (EC) [223498]
- U.S. National Institutes of Health [2P01AI060699-06A1, CRIPHHSN266200700010C]
- project EMPERIE (EC) [223498]
- Fundacion La Caixa
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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-Delta E) 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-Delta E resulted in decreased activation of NF-kappa B compared to levels for the wild-type virus. Most important, treatment with drugs that inhibited NF-kappa B 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-kappa B signaling pathway represents a major contribution to the inflammation induced after SARS-CoV infection and that NF-kappa B inhibitors are promising antivirals in infections caused by SARS-CoV and potentially other pathogenic human coronaviruses.
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