Viral-Infections cause dramatic changes in gene expression by mobilizing defined sets of transcriptional regulatory proteins. We speculate that Virus-Infection reprograms the human genome by inducing global transcriptional changes and alterations in chromatin structure. We aim to understand at the molecular level the mechanisms by which human cells reconfigure their genome in order to respond accurately to Viral-Infection signal(s) by applying genomics in naïve and infected human cell lines. Thus, we perform an holistic genome-wide study in distinct human cell lines to decode the molecular logic/mechanism that cells employ to switch on or off the appropriate battery of genes required for an efficient antiviral response.