As a zoonotic disease, ovine contagious pustular dermatitis (Orf) is a serious threat to sheep as well as humans. Orf virus (ORFV) interferon resistance protein (VIR) is the principal virulence protein that encodes a dsRNA-binding protein to inhibit host antiviral response. p53 is one of the key proteins of the host antiviral innate immunity. It not only enhances type I interferon secretion but also induces apoptosis in infected cells, and plays a crucial role in the immune response against various viral infections. However, it remains to be elucidated what role p53 plays in ORFV replication and whether ORFV's own protein VIR regulates p53 expression to promote self-replication. In this study, we showed that p53 has an antiviral effect on ORFV and can inhibit ORFV replication. In addition, ORFV nonstructural protein VIR interacts with p53 and degrades p53, which inhibits p53-mediated positive regulation of downstream antiviral genes. This study provides new insight into the immune evasion mediated by ORFV and identifies VIR as an antagonistic factor for ORFV to evade the antiviral response.

中文翻译：

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Orf病毒VIR拮抗p53介导的抗病毒作用，以促进病毒复制。

作为一种人畜共患病，绵羊的传染性脓疱性皮炎（Orf）对绵羊和人类均构成严重威胁。Orf病毒（ORFV）干扰素抗性蛋白（VIR）是主要毒力蛋白，其编码dsRNA结合蛋白以抑制宿主抗病毒应答。p53是宿主抗病毒先天免疫的关键蛋白之一。它不仅增强了I型干扰素的分泌，而且还诱导了感染细胞的凋亡，并且在针对各种病毒感染的免疫反应中起着至关重要的作用。然而，还有待阐明p53在ORFV复制中起什么作用，以及ORFV自身的蛋白VIR是否调节p53表达以促进自我复制。在这项研究中，我们表明p53对ORFV具有抗病毒作用，并且可以抑制ORFV复制。此外，ORFV非结构蛋白VIR与p53相互作用并降解p53，从而抑制p53介导的下游抗病毒基因的正调控。这项研究为ORFV介导的免疫逃逸提供了新的见解，并确定VIR是ORFV逃避抗病毒反应的拮抗因子。