This review will outline how the host cell metabolic regulators MYC, p53 and pRb/E2F can, in turn, be targeted by DNA tumor virus proteins expressed by human adenovirus (HAdV), human papillomavirus (HPV), Epstein–Barr virus (EBV) and Kaposi’s sarcoma-associated herpesvirus (KSHV) during infection or in virus-dependent cancers. The gene discussed is TP53; the disease is infection.