Cowpox Virus and Other Members of the Orthopoxvirus Genus Interfere with the Regulation of NF-κB Activation

AbstractNF-κB comprises a family of transcription factors that regulate key immune processes. In this study, the effects of orthopoxvirus infection upon the activation of NF-κB were examined. During the early phase of infection, cowpox virus can inhibit the induction of NF-κB-regulated gene expression by interfering with the process of IκBα degradation. Although either okadaic acid or tumor necrosis factor (TNF) treatment of infected cells can induce IκBα phosphorylation, further processing of IκBα is inhibited. These results suggest that cowpox virus is capable of inhibiting the activation of NF-κB at a point where multiple signal transduction pathways converge. Other orthopoxviruses affect NF-κB activity, but in a type-specific manner. Raccoonpox virus and vaccinia virus (Copenhagen strain) negatively affect NF-κB induction by TNF. In contrast, the modified vaccinia virus Ankara strain induces NF-κB activation, even in the absence of other stimuli. These findings suggest that orthopoxviruses may affect a broad range of virus–host interactions through their effects upon NF-κB activation. Moreover, because of the central role for NF-κB in immune processes and disease, these type-specific effects may contribute significantly to the immunogenic and pathogenic properties of poxviruses