Species-Specific Inhibition of Necroptosis by HCMV UL36
Viral infection activates cellular antiviral defenses including programmed cell death (PCD). Many viruses, particularly those of the <i>Herpesviridae</i> family, encode cell death inhibitors that antagonize different forms of PCD. While some viral inhibitors are broadly active in cells o...
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| Auteurs principaux: | , , , , |
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| Format: | article |
| Langue: | EN |
| Publié: |
MDPI AG
2021
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| Accès en ligne: | https://doaj.org/article/78a69bb246cd4b8da573c3db788e7c44 |
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| Résumé: | Viral infection activates cellular antiviral defenses including programmed cell death (PCD). Many viruses, particularly those of the <i>Herpesviridae</i> family, encode cell death inhibitors that antagonize different forms of PCD. While some viral inhibitors are broadly active in cells of different species, others have species-specific functions, probably reflecting the co-evolution of the herpesviruses with their respective hosts. Human cytomegalovirus (HCMV) protein UL36 is a dual cell death pathway inhibitor. It blocks death receptor-dependent apoptosis by inhibiting caspase-8 activation, and necroptosis by binding to the mixed lineage kinase domain-like (MLKL) protein and inducing its degradation. While UL36 has been shown to inhibit apoptosis in human and murine cells, the specificity of its necroptosis-inhibiting function has not been investigated. Here we show that UL36 interacts with both human and murine MLKL, but has a higher affinity for human MLKL. When expressed by a recombinant mouse cytomegalovirus (MCMV), UL36 caused a modest reduction of murine MLKL levels but did not inhibit necroptosis in murine cells. These data suggest that UL36 inhibits necroptosis, but not apoptosis, in a species-specific manner, similar to ICP6 of herpes simplex virus type 1 and MC159 of molluscum contagiosum virus. Species-specific necroptosis inhibition might contribute to the narrow host range of these viruses. |
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