Profiling kinase activity during hepatitis C virus replication using a wortmannin probe

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DOIResolve DOI: http://doi.org/10.1021/acsinfecdis.5b00083
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TypeArticle
Journal titleACS Infectious Diseases
ISSN2373-8227
Volume1
Issue9
Pages443452
SubjectActivity-based protein profiling; Hepatitis C; Host-virus interactions; Kinase probes; MAPK pathway; Wortmannin
AbstractTo complete its life cycle, the hepatitis C virus (HCV) induces changes to numerous aspects of its host cell. As kinases act as regulators of many pathways utilized by HCV, they are likely enzyme targets for virally induced inhibition or activation. Herein, we used activity-based protein profiling (ABPP), which allows for the identification of active enzymes in complex protein samples and the quantification of their activity, to identify kinases that displayed differential activity in HCV-expressing cells. We utilized an ABPP probe, wortmannin-yne, based on the kinase inhibitor wortmannin, which contains a pendant alkyne group for bioconjugation using bioorthogonal chemistry. We observed changes in the activity of kinases involved in the mitogen-activated protein kinase pathway, apoptosis pathways, and cell cycle control. These results establish changes to the active kinome, as reported by wortmannin-yne, in the proteome of human hepatoma cells actively replicating HCV. The observed changes include kinase activity that affect viral entry, replication, assembly, and secretion, implying that HCV is regulating the pathways that it uses for its life cycle through modulation of the active kinome.
Publication date
PublisherACS Publications
LanguageEnglish
AffiliationMedical Devices; NRC Steacie Institute for Molecular Sciences; National Research Council Canada
Peer reviewedYes
NPARC number23000358
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Record identifiere182d4b3-8569-4788-897c-9d5ac24cf5a0
Record created2016-07-08
Record modified2016-07-08
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