Early viral protein synthesis is necessary for NF-kappaB activation in modified vaccinia Ankara (MVA)-infected 293 T fibroblast cells.

Modified vaccinia Ankara (MVA) is an attenuated vaccinia virus, and is a promising vaccine vector for variola and monkeypox viruses, as well as for other pathogens. The MVA determinants important for vaccine efficacy and immunogenicity are poorly defined. MVA infection of fibroblast cells activates NF-kappaB, a characteristic not ascribed to wild-type vaccinia viruses. Thus, NF-kappaB activation, and the subsequent upregulation of host immune molecules, could be one of the determinants for MVA's immunogenicity. We report that ERK2 phosphorylation, an event preceding and required for NF-kappaB activation, occurred rapidly after virus infection. ERK2 and NF-kappaB remained inert when virus endocytosis was prevented, suggesting that virus-host cell interactions were insufficient for activating NF-kappaB. Inhibition of viral protein synthesis decreased NF-kappaB activation, and elimination of intermediate and late gene expression did not alter MVA-induced NF-kappaB activation. Thus, early gene expression activates NF-kappaB.