Differential gene expression in bovine cells infected with wild type and leaderless foot-and-mouth disease virus

The leader proteinase (Lpro) of foot-and-mouth disease virus (FMDV) plays a critical role in viral pathogenesis. Molecular studies have demonstrated that Lpro inhibits translation of host capped mRNAs and transcription of some genes involved in the innate immune response. We have used microarray technology to study the gene expression profile of bovine cells infected with wild type (WT) or leaderless FMDV. Thirty nine out of approximately 22,000 bovine genes were selectively up-regulated by 2 fold or more in leaderless versus WT virus infected cells. Most of the up-regulated genes corresponded to IFN-inducible genes, chemokines or transcription factors. Comparison of promoter sequences suggested that host factors NF-κB, ISGF3G and IRF1 specifically contributed to the differential expression, being NF-κB primarily responsible for the observed changes. Our results suggest that Lpro plays a central role in the FMDV evasion of the innate immune response by inhibiting NF-κB dependent gene expression.