AI Article Synopsis
- Necroptosis is a type of programmed cell death influenced by proteins RIP1 and RIP3, which form signaling complexes to trigger this process.
- The herpes simplex virus protein ICP6 interacts with RIP kinases, leading to necroptosis in infected mouse cells, thereby helping to limit the virus's spread.
- Contrary to its effect in mouse cells, ICP6 does not induce necroptosis in human cells and can inhibit necroptosis, suggesting that certain viral proteins can evolve to manipulate host cell death pathways to their advantage.
Article Abstract
Necroptosis is a form of programmed necrosis that is mediated by signaling complexes containing the receptor-interacting protein 3 (RIP3) and RIP1 kinases. We show that RIP3 and its interaction with the herpes simplex virus type 1 (HSV-1) protein ICP6 triggers necroptosis in infected mouse cells and limits viral propagation in mice. ICP6 interacts with RIP1/RIP3 through its RHIM domain and forms dimers/oliogmers by its C-terminal R1 domain. These binding events result in RIP1-RIP3 hetero- and RIP3-RIP3 homo-interactions and subsequent necroptosis of HSV-1-infected mouse cells. However, ICP6 RHIM cannot trigger necroptosis and even inhibits TNF-induced necroptosis in human cells. As the RHIM domain in murine cytomegalovirus protein vIRA can inhibit necroptosis in both human and mouse cells, these data suggest that both viral and host RHIM sequences determine whether the virus-host RHIM interaction is pro- or anti-necroptotic and that some viruses may evolve to escape this restriction.
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| http://dx.doi.org/10.1016/j.chom.2015.01.002 | DOI Listing |
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