HSV1 RIR1 binds RIPK3

During infection in human cells, herpes simplex virus (HSV)-1 and HSV-2 modulate cell death pathways using the large subunit (R1) of viral ribonucleotide reductase (RIR1 or UL39) (Dufour F et al. 2011; Guo H et al. 2015; Yu X et al. 2016; Ali M et al.2019). The N-terminal region of RIR1 protein carrying the RIP homotypic interaction motif (RHIM)-like element is sufficient for RHIM-dependent interaction with receptor‐interacting protein kinase 1 (RIPK1) and receptor‐interacting protein kinase 3 (RIPK3) thus inhibiting the interaction between RIPK1 and RIPK3 (Guo H et al. 2015; Yu X et al. 2015). An intact RHIM is required for the interaction between RIPK1 and RIPK3 that occurs downstream of tumour necrosis factor receptor 1 (TNFR1) activation during the programmed cell death response known as necroptosis (Sun X et al. 2002). In addition, the large carboxyl-terminal region of HSV RIR1 protein mediates the binding to caspase 8 (CASP8) (Dufour F et al. 2011; Guo H et al. 2015). HSV RIR1 is thought to block necroptosis in infected human cells by interactions with RIPK1, RIPK3 and CASP8 (Guo H et al. 2015; Mocarski ES et al. 2015).

在人类细胞感染过程中，单纯疱疹病毒-1 (HSV-1) 和 HSV-2 通过病毒核糖核苷酸还原酶的大亚基（R1）[RIR1 或 UL39](Dufour F et al. 2011; Guo H et al. 2015; Yu X et al. 2016; Ali M et al.2019)调节细胞死亡途径。RIR1蛋白的N端区域携带RIP同源相互作用基序（RHIM）样元件，足以与受体相互作用蛋白激酶1 (RIPK1) 和受体相互作用蛋白激酶3 (RIPK3) 发生RHIM依赖性相互作用，从而抑制RIPK1与RIPK3之间的相互作用（Guo H et al. 2015; Yu X et al. 2015）。维持RHIM结构的完整性对于肿瘤坏死因子受体1 (TNFR1) 激活后程序性细胞死亡反应即坏死性凋亡过程中RIPK1与RIPK3的相互作用至关重要（Sun X et al. 2002）。此外，HSV RIR1蛋白的大羧基末端区域介导与半胱氨酸蛋白酶8 (CASP8) 的结合（Dufour F et al. 2011; Guo H et al. 2015）。HSV RIR1被认为通过与其相互作用，包括RIPK1、RIPK3和CASP8，在感染的人类细胞中阻断坏死性凋亡（Guo H et al. 2015; Mocarski ES et al. 2015）。