{"doi":"10.3390/ijms18112346","title":"Modulation of Cell Death Pathways by Hepatitis C Virus Proteins in Huh7.5 Hepatoma Cells","abstract":"<jats:p>The hepatitis C virus (HCV) causes chronic liver disease leading to fibrosis, cirrhosis, and hepatocellular carcinoma. HCV infection triggers various types of cell death which contribute to hepatitis C pathogenesis. However, much is still unknown about the impact of viral proteins on them. Here we present the results of simultaneous immunocytochemical analysis of markers of apoptosis, autophagy, and necrosis in Huh7.5 cells expressing individual HCV proteins or their combinations, or harboring the virus replicon. Stable replication of the full-length HCV genome or transient expression of its core, Е1/Е2, NS3 and NS5B led to the death of 20–47% cells, 72 h posttransfection, whereas the expression of the NS4A/B, NS5A or NS3-NS5B polyprotein did not affect cell viability. HCV proteins caused different impacts on the activation of caspases-3, -8 and -9 and on DNA fragmentation. The structural core and E1/E2 proteins promoted apoptosis, whereas non-structural NS4A/B, NS5A, NS5B suppressed apoptosis by blocking various members of the caspase cascade. The majority of HCV proteins also enhanced autophagy, while NS5A also induced necrosis. As a result, the death of Huh7.5 cells expressing the HCV core was induced via apoptosis, the cells expressing NS3 and NS5B via autophagy-associated death, and the cells expressing E1/E2 glycoproteins or harboring HCV the replicon via both apoptosis and autophagy.</jats:p>","journal":"International Journal of Molecular Sciences","year":2017,"id":25724,"datarank":0.5767445985328093,"base_score":2.70805020110221,"endowment":2.70805020110221,"self_citation_contribution":0.40620753016533157,"citation_network_contribution":0.17053706836747776,"self_endowment_contribution":0.40620753016533157,"citer_contribution":0.17053706836747776,"corpus_percentile":null,"corpus_rank":null,"citation_count":14,"citer_count":10,"citers_with_citation_signal":9,"citers_with_endowment":9,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":150614,"name":"Ekaterina Lesnova","orcid":"0000-0002-2801-6843","position":1,"is_corresponding":false},{"id":150615,"name":"Pavel Solyev","orcid":"0000-0002-5546-4975","position":2,"is_corresponding":false},{"id":150616,"name":"Natalia Zakirova","orcid":null,"position":3,"is_corresponding":false},{"id":14511,"name":"Vladimir Prassolov","orcid":"0000-0002-2429-6649","position":4,"is_corresponding":false},{"id":150617,"name":"Sergey Kochetkov","orcid":null,"position":5,"is_corresponding":false},{"id":150618,"name":"Alexander Ivanov","orcid":"0000-0002-5659-9679","position":6,"is_corresponding":false},{"id":150619,"name":"Alla Kushch","orcid":"0000-0002-3396-5533","position":7,"is_corresponding":false},{"id":150613,"name":"Olga Masalova","orcid":"0000-0001-5571-5669","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"base_score":2.70805020110221,"endowment":2.70805020110221,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"29113144","pmcid":"PMC5713315","openalex_id":"https://openalex.org/W2767237799","authors":[],"funders":[{"funder_name":"Russian Foundation for Basic Research","grant_id":"17-04-01238","title":null},{"funder_name":"Russian Science Foundation","grant_id":"14-14-01021","title":null}],"total_grants":2,"fwci":0.7226,"citation_percentile":0.70912873,"influential_citations":0,"citation_trend":[{"year":2018,"count":2},{"year":2020,"count":3},{"year":2021,"count":3},{"year":2023,"count":2},{"year":2024,"count":2},{"year":2025,"count":2}],"oa_status":"gold","license":"cc-by","oa_locations":[{"url":"https://www.mdpi.com/1422-0067/18/11/2346/pdf?version=1509980096","host_type":"journal"},{"url":"https://www.mdpi.com/1422-0067/18/11/2346/pdf?version=1509980096","host_type":"GOLD"},{"url":"https://www.mdpi.com/1422-0067/18/11/2346/pdf?version=1509980096","host_type":"publisher"},{"url":"https://www.mdpi.com/1422-0067/18/11/2346/pdf","host_type":"publisher"},{"url":"https://doi.org/10.3390/ijms18112346","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/29113144","host_type":"repository"},{"url":"https://doaj.org/article/d3eca07f66034cb484751ce9c80bfae3","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/5713315","host_type":"repository"},{"url":"https://dx.doi.org/10.3390/ijms18112346","host_type":"repository"},{"url":"https://europepmc.org/articles/PMC5713315","host_type":"Europe_PMC"},{"url":"https://europepmc.org/articles/PMC5713315?pdf=render","host_type":"Europe_PMC"}],"fields_of_study":["Hepatitis C virus research","Autophagy in Disease and Therapy","Endoplasmic Reticulum Stress and Disease","Medicine","Biology","Apoptosis","Autophagy","Carcinoma, Hepatocellular","Caspases","Cell Line, Tumor","Gene Expression Regulation, Neoplastic","Genome, Viral","Hepacivirus","Hepatitis C","Humans","Liver Cirrhosis","Liver Neoplasms","Signal Transduction","Transfection","Viral Nonstructural Proteins","Virus Replication","RNA-Dependent RNA Polymerase"],"mesh_terms":["Autophagy","Hepatitis C","Carcinoma, Hepatocellular","Humans","Liver Cirrhosis","Liver Neoplasms","RNA-Dependent RNA Polymerase","Transfection","Virus Replication","Signal Transduction","Gene Expression Regulation, Neoplastic","Hepacivirus","Genome, Viral","Apoptosis","Viral Nonstructural Proteins","Caspases","Cell Line, Tumor"],"keywords":["NS5A","NS5B","Hepatitis C virus","NS3","Programmed cell death","NS2-3 protease","Apoptosis","Biology","Autophagy","Caspase","Virology","Replicon","Inhibitor of apoptosis","Virus","Cancer research","Cell biology","Molecular biology","Hepacivirus","Biochemistry","Gene","necrosis","Hepatoma Huh7.5 Cells"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Good health and well-being"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-06-08T07:27:46.288435Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}