Table 1.

Selected examples of viral strategies to target and circumvent the p53 pathway

Virus	Viral proteins involved	Interaction with p53	References
Influenza A virus (IAV)	NP	NP enhances p53 stabilization and apoptosis, enhancing virus release from infected cells	[12,14–15]
Zika virus (ZIKV)	ZCP	ZIKV triggers p53-induced cell death in neural cells and progenitors	[18,19]
HIV type 1 (HIV-1)	Nef Tat Vif	Nef may inhibit p53 function during early steps of viral replication; Vif may increase p53 function and contribute to cytopathic effects. Inhibition of SIRT1 by tat may modulate p53 acetylation and activation	[20–22]
Human herpes simplex virus 1 (HSV-1)	ICP0 ICP22 ICP27	ICP27 is a transcriptional target of p53. ICP0 targets HAUSP and enhances p53 degradation. p53 regulates ICP0 degradation. ICP22 prevents the negative regulation of ICP0 by p53	[23,24,25]
Epstein--Barr virus (EBV)	BZLF1 EBNA1 EBNA3C LMP1	BZLF1 induces Mdm2-independent p53 degradation. EBNA1 prevents p53 and Mdm2 degradation, modulating p53-dependent repair and apoptosis. EBNA3C repress DNA-binding and transcriptional activity. LMP1 promotes p53 accumulation and impair cell-cycle arrest and apoptosis	[26–28,29]
High -risk papilloma viruses (HPV 16, 18, 31, 45)	E6, E7	E6 binds E6AP and induces p53 degradation. Disruption of pRb by E7 abrogate p53 downregulation of DREAM	[30–31,33]
Hepatitis B virus (HBV)	HBx	HBx re-directs and re-wire p53 transcriptional activity. Mutant HBx form an oncogenic complex with mutant TP53 p.R249S	[35–36]
SARS-CoV viruses	Nsp2, nsp3	Nsp2 interacts with prohibitin (PHB) 1 and 2, involved mitochondrial biogenesis, causing ROS release and inducing p53 through DNA damage Nsp3 is a multidomain protein that binds and activates RCHY1, inducing Mdm2-independent p53 degradation	[4,13,46]