Modulation of gene expression in a human cell line caused by poliovirus, vacciniavirus and interferon

A human embryonic fibroblast cell line was synchronously infected with poliovirus in the absence or presence of interferon-α, or with vacciniavirus, a virus that is not inhibited by interferon. The titers were sufficient to yield productive infection in a majority of the cells. The cells were harvested in triplicate at various time-points, and the transcriptosome compared with mock infected cells using oligo-based 35 k microarrays. The project had two purposes: to characterize the cellular response and to look for candidate genes involved in viral defense. The changes in gene expression due to vaccinia virus did not correspond to those caused by poliovirus. More surprisingly, neither did the changes when comparing 8 h and 16 h of poliovirus infection. However, a large proportion of the genes up-regulated by interferon-α were also up-regulated by poliovirus, both at 8 h and 16 h. Interferon-α inhibited poliovirus replication, thus the observations suggest that the cells do launch an antiviral response to poliovirus. Moreover, as interferon genes were not induced, the data indicate that several of the relevant genes can be activated in an interferon independent manner. Further analyses of the data led to a list of candidate antiviral genes. Functional information was limited, or absent, for most of these genes. Keywords: Poliovirus; Vacciniavirus; Interferon; Microarray; Gene expression; Defense genes A human cell culture was used to investigate the response to viral infections. The cells were incubated for 1 h with either poliovirus or vacciniavirus, washed and incubated for another 4 to 16 h. Total RNA from three parallel cell cultures were used for each time point and compared with mock infected cells. Interferon-alpha, at a concentration sufficient to inhibit poliovirus replication, was used to help single out genes that might be involved in viral defence.