HSV1 RIR1 binds CASP8

Stable Identifier
R-HSA-9687458
Type
Reaction [binding]
Species
Homo sapiens
Related Species
Human herpesvirus 1
Compartment
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During infection in human cells, herpes simplex virus 1 (HSV1) and HSV2 modulate cell death pathways using the large subunit (R1) of viral ribonucleotide reductase (RIR1 or UL39) proteins (Dufour F et al. 2011; Guo H et al. 2015; Yu X et al. 2016; Ali M et al. 2019). The HSV1 and HSV2 RIR1 proteins suppress death receptor-dependent apoptosis by interacting with death effector domains of caspase 8 (CASP8) via a conserved C-terminal ribonucleotide reductase (RNR) domain (Dufour F et al. 2011). The ability of HSV1 RIR1 and HSV2 RIR1 to bind CASP8 is integral to their suppression activity against necroptosis in human cells. Necroptosis complements apoptosis as a host defense pathway to stop virus infection and is mediated by the interaction between receptor‐interacting protein kinase 1 (RIPK1) and RIPK3 that occurs downstream of tumor necrosis factor receptor 1 (TNFR1) activation during the programmed cell death response (Sun X et al. 2002). The N-terminal region of HSV1 and HSV2 RIR1 proteins carrying the RIP homotypic interaction motif (RHIM)-like element is sufficient for RHIM-dependent interaction with RIPK1 and RIPK3 thus inhibiting the interaction between RIPK1 and RIPK3 (Guo H et al. 2015; Yu X et al. 2015). HSV1 RIR1 and HSV2 RIR1 are thought to block the programmed cell death responses in infected human cells by interactions with RIPK1, RIPK3 and CASP8 (Guo H et al. 2015; Mocarski ES et al. 2015).

Literature References
PubMed ID Title Journal Year
25674983 Herpes simplex virus suppresses necroptosis in human cells

Guo, H, Omoto, S, Harris, PA, Finger, JN, Bertin, J, Gough, PJ, Kaiser, WJ, Mocarski, ES

Cell Host Microbe 2015
Participants
Participates
Event Information
Disease
Name Identifier Synonyms
viral infectious disease DOID:934 Viral disease, virus infection, virus infection
Authored
Reviewed
Created
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