title: Chemical proteomic identification of T-plastin as a novel host cell response factor in HCV infection.
abstract: Hepatitis C virus (HCV) infection is the leading cause of chronic liver disease that currently affects at least 170 million people worldwide. Although significant efforts have been focused on discovering inhibitors of a viral polymerase (NS5B) or protease (NS3), strategies to cure HCV infection have been hampered by the limited therapeutic target proteins. Thus, discovery of a novel target remains a major challenge. Here, we report a method that combines transcriptome expression analysis with unbiased proteome reactivity profiling to identify novel host cell response factors in HCV infection. A chemical probe for non-directed proteomic profiling was selected based on genome-wide transcriptome expression analysis after HCV infection, which revealed noticeable alterations related to disulfide bond metabolism. On the basis of this result, we screened the proteome reactivity using chemical probes containing thiol-reactive functional groups and discovered a unique labeling profile in HCV-infected cells. A subsequent quantitative chemical proteomic mapping study led to the identification of a target protein, T-plastin (PLST), and its regulation of HCV replication. Our approach demonstrates both a straightforward strategy for selecting chemical probes to discriminate disease states using a model system and its application for proteome reactivity profiling for novel biomarker discovery.
authors.affiliation: Molecular Recognition Research Center, Korea Institute of Science and Technology, 39-1 Hawolgok-dong, Seoul, 136-791, Republic of Korea.
authors.forename: Young-Hwa
authors.initials: YH
authors.lastname: Yoo
authors.affiliation: Molecular Recognition Research Center, Korea Institute of Science and Technology, 39-1 Hawolgok-dong, Seoul, 136-791, Republic of Korea.
authors.forename: JiHyeon
authors.initials: J
authors.lastname: Yun
authors.affiliation: Molecular Recognition Research Center, Korea Institute of Science and Technology, 39-1 Hawolgok-dong, Seoul, 136-791, Republic of Korea.
authors.forename: Chang No
authors.initials: CN
authors.lastname: Yoon
authors.affiliation: 1] Molecular Recognition Research Center, Korea Institute of Science and Technology, 39-1 Hawolgok-dong, Seoul, 136-791, Republic of Korea [2] Department of Biological Chemistry, University of Science &Technology, 113 Gwahank-ro, Yuseong-gu, Daejeon 305-333, Republic of Korea.
authors.forename: Jun-Seok
authors.initials: JS
authors.lastname: Lee
mesh_terms: D000477:Alkylating Agents / Q000737:chemistry; D001483:Base Sequence; D002460:Cell Line; D005838:Genotype; D016174:Hepacivirus / Q000235:genetics / Q000502:physiology; D006526:Hepatitis C / Q000378:metabolism / Q000473:pathology / Q000821:virology; D054884:Host-Pathogen Interactions; D006801:Humans; D007553:Isotope Labeling; D008562:Membrane Glycoproteins / Q000032:analysis* / Q000037:antagonists & inhibitors / Q000378:metabolism; D008840:Microfilament Proteins / Q000032:analysis* / Q000037:antagonists & inhibitors / Q000378:metabolism; D015335:Molecular Probes / Q000737:chemistry*; D016376:Oligonucleotides, Antisense / Q000378:metabolism; D020543:Proteome / Q000032:analysis / Q000737:chemistry*; D040901:Proteomics; D034622:RNA Interference; D014779:Virus Replication
chemical_list: D000477:Alkylating Agents; D008562:Membrane Glycoproteins; D008840:Microfilament Proteins; D015335:Molecular Probes; D016376:Oligonucleotides, Antisense; D020543:Proteome; C026742:plastin