| First Author | DeDiego ML | Year | 2014 |
| Journal | J Virol | Volume | 88 |
| Issue | 2 | Pages | 913-24 |
| PubMed ID | 24198408 | Mgi Jnum | J:286180 |
| Mgi Id | MGI:6400404 | Doi | 10.1128/JVI.02576-13 |
| Citation | DeDiego ML, et al. (2014) Inhibition of NF-kappaB-mediated inflammation in severe acute respiratory syndrome coronavirus-infected mice increases survival. J Virol 88(2):913-24 |
| abstractText | 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-DeltaE) 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-DeltaE resulted in decreased activation of NF-kappaB compared to levels for the wild-type virus. Most important, treatment with drugs that inhibited NF-kappaB 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-kappaB signaling pathway represents a major contribution to the inflammation induced after SARS-CoV infection and that NF-kappaB inhibitors are promising antivirals in infections caused by SARS-CoV and potentially other pathogenic human coronaviruses. |
