Immortalized hepatocyte-like cells: A competent hepatocyte model for studying clinical HCV isolate infection
3
Issued Date
2024-05-01
Resource Type
eISSN
19326203
Scopus ID
2-s2.0-85192936301
Pubmed ID
38739590
Journal Title
PLoS ONE
Volume
19
Issue
5 May
Rights Holder(s)
SCOPUS
Bibliographic Citation
PLoS ONE Vol.19 No.5 May (2024)
Suggested Citation
Pewkliang Y., Thongsri P., Suthivanich P., Thongbaiphet N., Keatkla J., Pasomsub E., Anurathapan U., Borwornpinyo S., Wongkajornsilp A., Hongeng S., Sa-Ngiamsuntorn K. Immortalized hepatocyte-like cells: A competent hepatocyte model for studying clinical HCV isolate infection. PLoS ONE Vol.19 No.5 May (2024). doi:10.1371/journal.pone.0303265 Retrieved from: https://repository.li.mahidol.ac.th/handle/123456789/98435
Title
Immortalized hepatocyte-like cells: A competent hepatocyte model for studying clinical HCV isolate infection
Corresponding Author(s)
Other Contributor(s)
Abstract
More than 58 million individuals worldwide are inflicted with chronic HCV. The disease carries a high risk of end stage liver disease, i.e., cirrhosis and hepatocellular carcinoma. Although direct-acting antiviral agents (DAAs) have revolutionized therapy, the emergence of drug-resistant strains has become a growing concern. Conventional cellular models, Huh7 and its derivatives were very permissive to only HCVcc (JFH-1), but not HCV clinical isolates. The lack of suitable host cells had hindered comprehensive research on patient-derived HCV. Here, we established a novel hepatocyte model for HCV culture to host clinically pan-genotype HCV strains. The immortalized hepatocyte-like cell line (imHC) derived from human mesenchymal stem cell carries HCV receptors and essential host factors. The imHC outperformed Huh7 as a host for HCV (JFH-1) and sustained the entire HCV life cycle of pan-genotypic clinical isolates. We analyzed the alteration of host markers (i.e., hepatic markers, cellular innate immune response, and cell apoptosis) in response to HCV infection. The imHC model uncovered the underlying mechanisms governing the action of IFN-α and the activation of sofosbuvir. The insights from HCV-cell culture model hold promise for understanding disease pathogenesis and novel anti-HCV development.