{"doi":"10.1126/sciadv.adj4198","title":"Hepatoviruses promote very-long-chain fatty acid and sphingolipid synthesis for viral RNA replication and quasi-enveloped virus release","abstract":"Virus-induced changes in host lipid metabolism are an important but poorly understood aspect of viral pathogenesis. By combining nontargeted lipidomics analyses of infected cells and purified extracellular quasi-enveloped virions with high-throughput RNA sequencing and genetic depletion studies, we show that hepatitis A virus, an hepatotropic picornavirus, broadly manipulates the host cell lipid environment, enhancing synthesis of ceramides and other sphingolipids and transcriptionally activating acyl-coenzyme A synthetases and fatty acid elongases to import and activate long-chain fatty acids for entry into the fatty acid elongation cycle. Phospholipids with very-long-chain acyl tails (>C22) are essential for genome replication, whereas increases in sphingolipids support assembly and release of quasi-enveloped virions wrapped in membranes highly enriched for sphingomyelin and very-long-chain ceramides. Our data provide insight into how a pathogenic virus alters lipid flux in infected hepatocytes and demonstrate a distinction between lipid species required for viral RNA synthesis versus nonlytic quasi-enveloped virus release.","journal":"Science Advances","year":2023,"id":334851,"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":21,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9537,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1063779,"name":"Zhucui Li","orcid":"0000-0002-1771-972X","position":1,"is_corresponding":false},{"id":510177,"name":"Guan‐Yuan Chen","orcid":"0000-0002-0505-4089","position":2,"is_corresponding":false},{"id":520807,"name":"Kevin L. McKnight","orcid":"0000-0002-9099-2044","position":3,"is_corresponding":false},{"id":599624,"name":"Takayoshi Shirasaki","orcid":"0000-0001-9756-8935","position":4,"is_corresponding":false},{"id":1063780,"name":"Bryan Yonish","orcid":"0009-0005-9790-5774","position":5,"is_corresponding":false},{"id":1064247,"name":"Heyjeong Kim","orcid":null,"position":6,"is_corresponding":false},{"id":5946,"name":"Ethan J. Fritch","orcid":"0000-0003-1096-8958","position":7,"is_corresponding":false},{"id":5953,"name":"Timothy P. Sheahan","orcid":"0000-0001-9181-2183","position":8,"is_corresponding":false},{"id":392341,"name":"Masamichi Muramatsu","orcid":"0000-0002-0153-3533","position":9,"is_corresponding":false},{"id":592285,"name":"Maryna Kapustina","orcid":"0000-0002-6906-4163","position":10,"is_corresponding":false},{"id":555983,"name":"Craig E. Cameron","orcid":"0000-0002-7564-5642","position":11,"is_corresponding":false},{"id":520808,"name":"You Li","orcid":"0000-0001-5458-6009","position":12,"is_corresponding":false},{"id":336554,"name":"Qibin Zhang","orcid":"0000-0002-6135-8706","position":13,"is_corresponding":false},{"id":415265,"name":"Stanley M. Lemon","orcid":"0000-0003-1450-806X","position":14,"is_corresponding":false},{"id":948177,"name":"Tomoyuki Shiota","orcid":"0000-0001-8133-9521","position":0,"is_corresponding":true}],"reference_count":65,"raw_metadata":null,"created_at":"2026-07-19T01:09:53.742667Z","pmid":"37862421","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":[]}