Cargando…

Human Rhinovirus 3C protease cleaves RIPK1, concurrent with caspase 8 activation

Human Rhinovirus (HRV) is a pathogen of significant medical importance, being a major cause of upper respiratory tract infections (common colds) as well as causing the majority of virus-induced asthma exacerbations. We investigated whether HRV could modulate apoptosis, an innate antiviral response....

Descripción completa

Detalles Bibliográficos
Autores principales: Croft, Sarah N., Walker, Erin J., Ghildyal, Reena
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5785518/
https://www.ncbi.nlm.nih.gov/pubmed/29371673
http://dx.doi.org/10.1038/s41598-018-19839-4
_version_ 1783295621895028736
author Croft, Sarah N.
Walker, Erin J.
Ghildyal, Reena
author_facet Croft, Sarah N.
Walker, Erin J.
Ghildyal, Reena
author_sort Croft, Sarah N.
collection PubMed
description Human Rhinovirus (HRV) is a pathogen of significant medical importance, being a major cause of upper respiratory tract infections (common colds) as well as causing the majority of virus-induced asthma exacerbations. We investigated whether HRV could modulate apoptosis, an innate antiviral response. Apoptotic signals are generated either extrinsically or intrinsically and are propagated via caspase cascades that lead to cell death, reducing viral replication, which relies on cellular machinery. Using HRV16 infected cells, in combination with chemical inducers and inhibitors of extrinsic apoptosis we show that HRV16 3C protease cleaves a key intermediate in extrinsic apoptosis. Receptor-interacting protein kinase-1 (RIPK1), an extrinsic apoptosis adaptor protein, was cleaved by caspase 8, as expected, during chemical induction of apoptosis. RIPK1 was cleaved in HRV infection albeit at a different site. Caspase 8 activation, which is associated with extrinsic apoptosis, was concurrent with HRV 3C protease mediated cleavage of RIPK1, and potentially increased the accessibility of the HRV 3C cleavage site within RIPK1 in-vitro. The caspase 8 mediated RIPK1 cleavage product has a pro-apoptotic function, and further cleavage of this pro-apoptotic cleavage product by HRV 3C may provide a mechanism by which HRV limits apoptosis.
format Online
Article
Text
id pubmed-5785518
institution National Center for Biotechnology Information
language English
publishDate 2018
publisher Nature Publishing Group UK
record_format MEDLINE/PubMed
spelling pubmed-57855182018-02-07 Human Rhinovirus 3C protease cleaves RIPK1, concurrent with caspase 8 activation Croft, Sarah N. Walker, Erin J. Ghildyal, Reena Sci Rep Article Human Rhinovirus (HRV) is a pathogen of significant medical importance, being a major cause of upper respiratory tract infections (common colds) as well as causing the majority of virus-induced asthma exacerbations. We investigated whether HRV could modulate apoptosis, an innate antiviral response. Apoptotic signals are generated either extrinsically or intrinsically and are propagated via caspase cascades that lead to cell death, reducing viral replication, which relies on cellular machinery. Using HRV16 infected cells, in combination with chemical inducers and inhibitors of extrinsic apoptosis we show that HRV16 3C protease cleaves a key intermediate in extrinsic apoptosis. Receptor-interacting protein kinase-1 (RIPK1), an extrinsic apoptosis adaptor protein, was cleaved by caspase 8, as expected, during chemical induction of apoptosis. RIPK1 was cleaved in HRV infection albeit at a different site. Caspase 8 activation, which is associated with extrinsic apoptosis, was concurrent with HRV 3C protease mediated cleavage of RIPK1, and potentially increased the accessibility of the HRV 3C cleavage site within RIPK1 in-vitro. The caspase 8 mediated RIPK1 cleavage product has a pro-apoptotic function, and further cleavage of this pro-apoptotic cleavage product by HRV 3C may provide a mechanism by which HRV limits apoptosis. Nature Publishing Group UK 2018-01-25 /pmc/articles/PMC5785518/ /pubmed/29371673 http://dx.doi.org/10.1038/s41598-018-19839-4 Text en © The Author(s) 2018 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Croft, Sarah N.
Walker, Erin J.
Ghildyal, Reena
Human Rhinovirus 3C protease cleaves RIPK1, concurrent with caspase 8 activation
title Human Rhinovirus 3C protease cleaves RIPK1, concurrent with caspase 8 activation
title_full Human Rhinovirus 3C protease cleaves RIPK1, concurrent with caspase 8 activation
title_fullStr Human Rhinovirus 3C protease cleaves RIPK1, concurrent with caspase 8 activation
title_full_unstemmed Human Rhinovirus 3C protease cleaves RIPK1, concurrent with caspase 8 activation
title_short Human Rhinovirus 3C protease cleaves RIPK1, concurrent with caspase 8 activation
title_sort human rhinovirus 3c protease cleaves ripk1, concurrent with caspase 8 activation
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5785518/
https://www.ncbi.nlm.nih.gov/pubmed/29371673
http://dx.doi.org/10.1038/s41598-018-19839-4
work_keys_str_mv AT croftsarahn humanrhinovirus3cproteasecleavesripk1concurrentwithcaspase8activation
AT walkererinj humanrhinovirus3cproteasecleavesripk1concurrentwithcaspase8activation
AT ghildyalreena humanrhinovirus3cproteasecleavesripk1concurrentwithcaspase8activation