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Viral strategies for circumventing p53: the case of severe acute respiratory syndrome coronavirus. Current opinion in oncology

Emily

Editor, Senior Moderator
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7924916/#
Cardozo, C. M., & Hainaut, P. (2021). Viral strategies for circumventing p53: the case of severe acute respiratory syndrome coronavirus. Current opinion in oncology, 33(2), 149?158. https://doi.org/10.1097/CCO.0000000000000713

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With respect to cancer risk, it should be noted the molecular mechanisms used by SARS viruses to impair p53 bear similarities with those leveraged by several DNA or RNA viruses with transforming potential. Such mechanisms, consisting in the targeting of various p53 degradation mechanisms by viral proteins, are utilized by members of the Herpes virus family, by EBV as well as by HR HPVs. In the latter case, long-term inhibition of p53 via persistent E6-mediated degradation has similar functional consequences as TP53 inactivating mutation. Whereas the p53 impairment mediated by SARS-CoV nsp3 is supposed to be short-lived, it implies that during a certain amount of time, cells may be deprived from the capacity of p53 to act as a guardian of the genome against oncogenic DNA damage, despite being exposed to a high level of potentially oncogenic stress. Of note, the duration of SARS-CoV-2 infection is still not definitively evaluated. Several studies have evoked the possibility that SARS-CoV-2 may become persistent into some tissues, with diverse consequences regarding long-term effects of infection [49?50]. Regarding SARS-CoV-1, proximal tubular epithelial cells of the kidney have been suggested to be a site of productive and persistent viral replication favoring the emergence of viral variants [51]. However, in the case of SARS-CoV-2, there is currently no experimental evidence of long-term persistence and this question needs to be further assessed. Considering the specificity and power of the weapons deployed by SARS viruses to target p53, this hypothesis cannot be just brushed aside. The public health implications would be major and would require that infected patients would be cautiously monitored over a long period of time.
 
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