A Second Career for p53 as A Broad-Spectrum Antiviral?

As the world exits the global pandemic caused by the previously unknown SARS-CoV-2, we also mark the 30th anniversary of p53 being named "molecule of the year" by Science based on its role as a tumor suppressor. Although p53 was originally discovered in association with a viral protein, studies on its role in preventing carcinogenesis have far overshadowed research related to p53 ' s role in viral infections. Nonetheless, there is an extensive body of scientific literature demonstrating that p53 is a critical component of host immune responses to viral infections. It is striking that diverse viruses have independently developed an impressive repertoire of varied mechanisms to counter the host defenses that are mediated by and through p53. The variety of ways developed by viruses to disrupt p53 in their hosts attests to the protein's importance in combatting viral pathogens. The present perspective aims to make the case that p53 ought to be considered a virus suppressor in addition to a tumor suppressor. It is hoped that additional research aimed at more fully understanding the role of p53 in antiviral immunity will result in the world being better positioned for the next pandemic than it was when SARS-CoV-2 emerged to produce COVID-19.