Necroptosis complements apoptosis as a host defense pathway to stop virus infection. 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).
Zheng, C, Yu, X, Yang, C, Li, Y, Jiang, X, Chen, Q, Su, C, Zhang, Z, Gong, L, He, S, Hou, J, Zhou, J, Hu, Z
Mocarski, ES, Finger, JN, Omoto, S, Kaiser, WJ, Guo, H, Bertin, J, Gough, PJ, Harris, PA
© 2022 Reactome
