p53 is not only a major tumor suppressor protein in vertebrates but is also involved in chronic inflammation [64], and plays a significant role in the innate immune response against virus infection [65,66,67] via several pathways including Toll-like receptor 3 (TLR3) [68], IFN regulatory factor 9 [69] and ubiquitin-like protein interferon-stimulated gene 15 (ISG15) [70]. This evidence concerns the gene ISG15 and viral infectious disease.