Targeting ectromelia virus and TNF/NF-κB or STAT3 signaling for effective treatment of viral pneumonia

Abstract

SignificanceAntivirals are ineffective in treating viral pneumonia if administered after 48 h post onset of disease symptoms. Lung pathology during respiratory viral infections is triggered by the host inflammatory response and tissue damage caused by replicating virus. Therefore, targeting both virus and inflammation would be more effective in treating pneumonia. Simultaneous treatment with an anti-inflammatory drug targeting TNF or STAT3 combined with an antiviral drug significantly improved clinical disease, reduced lung viral load and pathology and protected mice from severe pneumonia caused by respiratory ectromelia virus infection. The combined treatment suppressed multiple proinflammatory cytokines and cytokine-signaling pathways, including NF-κB and STAT3. Late after onset of symptoms, antiviral treatment alone cannot ameliorate viral pneumonia, as it cannot reduce inflammation effectively.