Global transcriptional analysis of model of persistent FMDV infection reveals critical role of host cells in persistence.

With the aid of ammonium chloride, we established a model for persistent foot-and-mouth disease virus (FMDV) infection of BHK-21 cells (Huang et al., 2011). Distinctive to a previously established model, the persistently infected cell line acquired new features including more rounded morphology, resistance to wild type FMDV infection, consistent replication efficiency in late passages, etc. To elucidate the mechanism of establishment of persistence, we performed systematically microarray analysis of gene expression profiles of acute and persistent infections and real-time quantitative PCR validation of key genes. Our results showed 12 common genes were found to be up-regulated in acute infection while down-regulated in persistent infection. Gene expression analysis indicated differences in the KEGG pathway, revealing important roles of host factors in the maintenance of symbiotic environment. The results suggest that, in contrast to previous viral persistence system, the critical element in establishment of the persistence in our lab is the evolution of host cells which regulate genome transcription to defy the lytic effects of FMDV infection.