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

Sarah N Croft, Erin J Walker, Reena Ghildyal

Research output: Contribution to journalArticle

3 Citations (Scopus)
4 Downloads (Pure)

Abstract

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.

Original languageEnglish
Article number1569
Number of pages11
JournalScientific Reports
Volume8
Issue number1
DOIs
Publication statusPublished - 25 Jan 2018

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Receptor-Interacting Protein Serine-Threonine Kinases
Caspase 8
Rhinovirus
Protein Kinases
Apoptosis
Common Cold
Caspases
3C proteases
Respiratory Tract Infections
Antiviral Agents
Cell Death
Asthma
Viruses
Infection

Cite this

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abstract = "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.",
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Human Rhinovirus 3C protease cleaves RIPK1, concurrent with caspase 8 activation. / Croft, Sarah N; Walker, Erin J; Ghildyal, Reena.

In: Scientific Reports, Vol. 8, No. 1, 1569, 25.01.2018.

Research output: Contribution to journalArticle

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