Cargando…
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 Herpesviridae family, encode cell death inhibitors that antagonize different forms of PCD. While some viral inhibitors are broadly active in cells of different species...
Autores principales: | , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8621378/ https://www.ncbi.nlm.nih.gov/pubmed/34834942 http://dx.doi.org/10.3390/v13112134 |
_version_ | 1784605443398565888 |
---|---|
author | Muscolino, Elena Castiglioni, Claudia Brixel, Renke Frascaroli, Giada Brune, Wolfram |
author_facet | Muscolino, Elena Castiglioni, Claudia Brixel, Renke Frascaroli, Giada Brune, Wolfram |
author_sort | Muscolino, Elena |
collection | PubMed |
description | Viral infection activates cellular antiviral defenses including programmed cell death (PCD). Many viruses, particularly those of the Herpesviridae 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. |
format | Online Article Text |
id | pubmed-8621378 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-86213782021-11-27 Species-Specific Inhibition of Necroptosis by HCMV UL36 Muscolino, Elena Castiglioni, Claudia Brixel, Renke Frascaroli, Giada Brune, Wolfram Viruses Article Viral infection activates cellular antiviral defenses including programmed cell death (PCD). Many viruses, particularly those of the Herpesviridae 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. MDPI 2021-10-22 /pmc/articles/PMC8621378/ /pubmed/34834942 http://dx.doi.org/10.3390/v13112134 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Muscolino, Elena Castiglioni, Claudia Brixel, Renke Frascaroli, Giada Brune, Wolfram Species-Specific Inhibition of Necroptosis by HCMV UL36 |
title | Species-Specific Inhibition of Necroptosis by HCMV UL36 |
title_full | Species-Specific Inhibition of Necroptosis by HCMV UL36 |
title_fullStr | Species-Specific Inhibition of Necroptosis by HCMV UL36 |
title_full_unstemmed | Species-Specific Inhibition of Necroptosis by HCMV UL36 |
title_short | Species-Specific Inhibition of Necroptosis by HCMV UL36 |
title_sort | species-specific inhibition of necroptosis by hcmv ul36 |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8621378/ https://www.ncbi.nlm.nih.gov/pubmed/34834942 http://dx.doi.org/10.3390/v13112134 |
work_keys_str_mv | AT muscolinoelena speciesspecificinhibitionofnecroptosisbyhcmvul36 AT castiglioniclaudia speciesspecificinhibitionofnecroptosisbyhcmvul36 AT brixelrenke speciesspecificinhibitionofnecroptosisbyhcmvul36 AT frascaroligiada speciesspecificinhibitionofnecroptosisbyhcmvul36 AT brunewolfram speciesspecificinhibitionofnecroptosisbyhcmvul36 |