{"doi":"10.3390/v13040613","title":"Role of Small Envelope Protein in Sustaining the Intracellular and Extracellular Levels of Hepatitis B Virus Large and Middle Envelope Proteins","abstract":"Hepatitis B virus (HBV) expresses co-terminal large (L), middle (M), and small (S) envelope proteins. S protein drives virion and subviral particle secretion, whereas L protein inhibits subviral particle secretion but coordinates virion morphogenesis. We previously found that preventing S protein expression from a subgenomic construct eliminated M protein. The present study further examined impact of S protein on L and M proteins. Mutations were introduced to subgenomic construct of genotype A or 1.1 mer replication construct of genotype A or D, and viral proteins were analyzed from transfected Huh7 cells. Mutating S gene ATG to prevent expression of full-length S protein eliminated M protein, reduced intracellular level of L protein despite its blocked secretion, and generated a truncated S protein through translation initiation from a downstream ATG. Truncated S protein was secretion deficient and could inhibit secretion of L, M, S proteins from wild-type constructs. Providing full-length S protein in trans rescued L protein secretion and increased its intracellular level from mutants of lost S gene ATG. Lost core protein expression reduced all the three envelope proteins. In conclusion, full-length S protein could sustain intracellular and extracellular L and M proteins, while truncated S protein could block subviral particle secretion.","journal":"Viruses","year":2021,"id":184805,"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":10,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9511,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":226636,"name":"Yongxiang Wang","orcid":"0000-0002-8832-7301","position":1,"is_corresponding":false},{"id":543168,"name":"Shuwen Fu","orcid":null,"position":2,"is_corresponding":false},{"id":542492,"name":"Quan Yuan","orcid":"0000-0001-5487-561X","position":3,"is_corresponding":false},{"id":30803,"name":"Qianru Wang","orcid":"0000-0002-7219-7522","position":4,"is_corresponding":false},{"id":345205,"name":"Ningshao Xia","orcid":"0000-0003-0179-5266","position":5,"is_corresponding":false},{"id":303205,"name":"Yu‐Mei Wen","orcid":null,"position":6,"is_corresponding":false},{"id":543169,"name":"Jisu Li","orcid":null,"position":7,"is_corresponding":false},{"id":542493,"name":"Shuping Tong","orcid":"0000-0002-9707-8538","position":8,"is_corresponding":false},{"id":740207,"name":"Jing Zhang","orcid":"0000-0003-2966-9149","position":0,"is_corresponding":true}],"reference_count":34,"raw_metadata":null,"created_at":"2026-07-18T23:48:30.970730Z","pmid":"33918367","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":[]}