Herpes simplex virus suppresses necroptosis in human cells

Hongyan Guo, Shinya Omoto, Philip A. Harris, Joshua N. Finger, John Bertin, Peter J. Gough, William J. Kaiser, Edward S. Mocarski

Resultado de la investigación: Articlerevisión exhaustiva

181 Citas (Scopus)

Resumen

Herpes simplex virus (HSV)-1 and HSV-2 are significant human pathogens causing recurrent disease. During infection, HSV modulates cell death pathways using the large subunit (R1) of ribonucleotide reductase (RR) to suppress apoptosis by binding to and blocking caspase-8. Here, we demonstrate that HSV-1 and HSV-2 R1 proteins (ICP6 and ICP10, respectively) also prevent necroptosis in human cells by inhibiting the interaction between receptor-interacting protein kinase 1 (RIP1) and RIP3, a key step in tumor necrosis factor (TNF)-induced necroptosis. We show that suppression of this cell death pathway requires an N-terminal RIP homotypic interaction motif (RHIM) within R1, acting in concert with the caspase-8-binding domain, which unleashes necroptosis independent of RHIM function. Thus, necroptosis is a human host defense pathway against two important viral pathogens that naturally subvert multiple death pathways via a single evolutionarily conserved gene product.

Idioma originalEnglish (US)
Páginas (desde-hasta)243-251
Número de páginas9
PublicaciónCell Host and Microbe
Volumen17
N.º2
DOI
EstadoPublished - feb. 11 2015
Publicado de forma externa

ASJC Scopus subject areas

  • Parasitology
  • Microbiology
  • Virology

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