{"doi":"10.3390/biom15010057","title":"Ethanol Disrupts the Protective Crosstalk Between Macrophages and HBV-Infected Hepatocytes","abstract":"About 296 million people worldwide are living with chronic hepatitis B viral (HBV) infection, and outcomes to end-stage liver diseases are potentiated by alcohol. HBV replicates in hepatocytes, but other liver non-parenchymal cells can sense the virus. In this study, we aimed to investigate the regulatory effects of macrophages on HBV marker and interferon-stimulated genes (ISGs) expressions in hepatocytes. This study was performed on HBV-replicating HepG2.2.15 cells and human monocyte-derived macrophages (MDMs). We found that exposure of HepG2.2.15 cells to an acetaldehyde-generating system (AGS) increased HBV RNA, HBV DNA, and cccDNA expressions and suppressed the activation of ISGs, APOBEC3G, ISG15, and OAS1. Supernatants collected from IFNα-activated MDMs decreased HBV marker levels and induced ISG activation in AGS-treated and untreated HepG2.215 cells. These effects were reversed by exposure of MDMs to ethanol and mimicked by treatment with exosome release inhibitor GW4869. We conclude that exosome-mediated crosstalk between IFN-activated macrophages and HBV-replicating hepatocytes plays a protective role via the up-regulation of ISGs and suppression of HBV replication. However, ethanol exposure to macrophages breaks this protection.","journal":"Biomolecules","year":2025,"id":539964,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":2,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9629,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":267278,"name":"Anup S. Pathania","orcid":"0000-0002-1517-2919","position":1,"is_corresponding":false},{"id":1427874,"name":"Grace Bybee","orcid":null,"position":2,"is_corresponding":false},{"id":381663,"name":"Kusum K. Kharbanda","orcid":"0000-0001-7759-8889","position":3,"is_corresponding":false},{"id":395979,"name":"Larisa Y. Poluektova","orcid":"0000-0001-7339-8732","position":4,"is_corresponding":false},{"id":387753,"name":"Natalia A. Osna","orcid":"0000-0001-7498-0556","position":5,"is_corresponding":false},{"id":395977,"name":"Murali Ganesan","orcid":"0000-0002-2981-568X","position":0,"is_corresponding":true}],"reference_count":32,"raw_metadata":null,"created_at":"2026-07-19T02:52:34.520788Z","pmid":"39858451","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":[]}