Interference with p53 functions in human viral infections, a target for novel antiviral strategies?

Abstract

Viral infections cause a major stress in host cells. The cellular responses to stress are mediated by p53, which by deregulation of cell cycle and apoptosis, may also be part of the host cell reaction to fight infections. Therefore, during evolutionary viral adaptation to host organisms, viruses have developed strategies to manipulate host cell p53 dependent pathways to facilitate their viral life cycles. Thus, interference with p53 function is an important component in viral pathogenesis. Many viruses have proteins that directly affect p53, while others alter the regulation of p53 in an indirect manner, mediated by hdm2 or akt, or induction of interferon. Rescue of p53 activity is becoming an area of therapeutic development in oncology. It might be feasible that manipulation of p53 mediated responses can become a therapeutic option to limit viral replication or dissemination. In this report, the mechanisms by which viral proteins manipulate p53 responses are reviewed, and it is proposed that a pharmacological rescue of p53 functions might help to control viral infections.