TNF-α exerts potent anti-rotavirus effects via the activation of classical NF-κB pathway

Active virus-host interactions determine the outcome of pathogen invasions. It has been shown that in isolated dendritic cells (DCs), rotavirus can induce the expression of tumor necrosis factor a (TNF-alpha), a vital cytokine mediating host immune responses. However, the role of TNF-alpha in rotavirus infection is unknown. In this study, we demonstrated that TNF-alpha has potent anti-rotavirus effects, independent of type I interferon production. Blocking of TNF-alpha by infliximab, a clinically available TNF alpha antibody, totally abrogated this effect. Mechanistic studies revealed that the anti-rotavirus effect of TNF-alpha was achieved by NF kappa B-regulated genes via the activation of classical nuclear factor kappa B (NF-kappa B) signaling. Our study reveals the pivotal role and the mechanism-of-actions of TNF-alpha in the host defense against rotavirus. Thus, this knowledge may contribute to the better understanding of the complexity of rotavirus-host interactions.