Transcriptional role of p53 in interferon-mediated antiviral immunity

Muñoz-Fontela, C. et al. J Exp Med. 205, 1929-38 (2008)

Speaker: 盧怡恬                                                 Time: 13:10~14:00, Oct. 8, 2008

Commentator: 張堯 老師                                            Place: Room 601

Abstract:

        P53, as a tumor suppressor, can respond to many signals that cause cellular stress, including DNA damage and oncogene expression. Previous studies indicate that p53 is also activated by type I interferon (IFN) in response to viral infections as a downstream target of type I IFN signaling.¹Type I IFN is recognized as a key component of the innate immune response and the first line of defence against viral infection.^2,3 Moreover, not only oncogenic viruses but also RNA viruses such as polioviruses have evolved mechanism designed to abrogate p53 responses. In this study, the authors investigated the role of p53 in antiviral immune response. They observed the inhibitory effect of p53 on early viral replication in infected mouse and human cells. Their findings suggested that p53 was sufficient to enhance IFN signaling through the induction of genes containing IFN-stimulated response elements both in vitro and in vivo. They also found that p53 enhanced IFN production in response to viral infection. In addition, the link between IFN signaling and production was dependent to a great deal on the p53-induced IFN regulatory factor 9 (IRF9). As part of the IFN-stimulated gene factor 3 complex, IRF9 was involved in a positive feedback of IFN production. Thus p53 is involved in innate immunity through enhancing the IFN-dependent antiviral state independent of its proapoptotic function.

References:

1.     Takaoka, A. et al. Integration of interferon-alpha/beta signalling to p53 responses in tumour suppression and antiviral defence. Nature. 424, 516-523 (2003).

2.     Pampin, M. et al. Cross talk between PML and p53 during poliovirus infection: implications for antiviral defense. J. Virol. 80, 8582-8592 (2006).

3.     Muñoz-Fontela, C. et al. Resistance to viral infection of super p53 mice. Oncogene. 24, 3059-3062 (2005).