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

Research output: Contribution to journalArticlepeer-review

137 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)243-251
Number of pages9
JournalCell Host and Microbe
Issue number2
StatePublished - Feb 11 2015
Externally publishedYes

ASJC Scopus subject areas

  • Parasitology
  • Microbiology
  • Virology


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