{"doi":"10.1128/jvi.00142-19","title":"Mutations That Increase the Stability of the Postfusion gp41 Conformation of the HIV-1 Envelope Glycoprotein Are Selected by both an X4 and R5 HIV-1 Virus To Escape Fusion Inhibitors Corresponding to Heptad Repeat 1 of gp41, but the gp120 Adaptive Mutations Differ between the Two Viruses","abstract":"<jats:p>HIV-1 fuses with cells when the gp41 subunit of Env refolds into a 6HB after binding to cellular receptors. Peptides corresponding to HR1 or HR2 interrupt gp41 refolding and inhibit HIV infection. Previously, we found that a CCR5 coreceptor-tropic HIV-1 acquired a key HR1 or HR2 resistance mutation to escape HR1 peptide inhibitors but only the key HR1 mutation to escape a trimer-stabilized HR1 peptide inhibitor. Here, we report that a CXCR4 coreceptor-tropic HIV-1 selected the same key HR1 or HR2 mutations to escape inhibition by the HR1 peptide but different combinations of HR1 and HR2 mutations to escape the trimer-stabilized HR1 peptide. All gp41 mutations enhance 6HB stability to outcompete inhibitors, but gp120 adaptive mutations differed between these R5 and X4 viruses, providing new insights into gp120-gp41 functional interactions affecting Env refolding during HIV entry.</jats:p>","journal":"Journal of Virology","year":2019,"id":617174,"datarank":0.2813831155918825,"base_score":1.791759469228055,"endowment":1.791759469228055,"self_citation_contribution":0.26876392038420827,"citation_network_contribution":0.01261919520767423,"self_endowment_contribution":0.26876392038420827,"citer_contribution":0.01261919520767423,"corpus_percentile":null,"corpus_rank":null,"citation_count":5,"citer_count":2,"citers_with_citation_signal":1,"citers_with_endowment":1,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":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":804246,"name":"Russell Vassell","orcid":"0000-0002-2295-5890","position":1,"is_corresponding":false},{"id":56399,"name":"Chen Yuan","orcid":"0000-0002-0708-9648","position":2,"is_corresponding":false},{"id":1591467,"name":"Paul W. Keller","orcid":null,"position":3,"is_corresponding":false},{"id":1591469,"name":"Hong Ling","orcid":null,"position":4,"is_corresponding":false},{"id":542963,"name":"Wei Wang","orcid":"0000-0001-8676-1190","position":5,"is_corresponding":false},{"id":804247,"name":"Carol D. Weiss","orcid":"0000-0002-9965-1289","position":6,"is_corresponding":false},{"id":433867,"name":"Min Zhuang","orcid":"0000-0001-6215-5807","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Mutations That Increase the Stability of the Postfusion gp41 Conformation of the HIV-1 Envelope Glycoprotein Are Selected by both an X4 and R5 HIV-1 Virus To Escape Fusion Inhibitors Corresponding to Heptad Repeat 1 of gp41, but the gp120 Adaptive Mutations Differ between the Two Viruses","abstract":"<jats:p>HIV-1 fuses with cells when the gp41 subunit of Env refolds into a 6HB after binding to cellular receptors. Peptides corresponding to HR1 or HR2 interrupt gp41 refolding and inhibit HIV infection. Previously, we found that a CCR5 coreceptor-tropic HIV-1 acquired a key HR1 or HR2 resistance mutation to escape HR1 peptide inhibitors but only the key HR1 mutation to escape a trimer-stabilized HR1 peptide inhibitor. Here, we report that a CXCR4 coreceptor-tropic HIV-1 selected the same key HR1 or HR2 mutations to escape inhibition by the HR1 peptide but different combinations of HR1 and HR2 mutations to escape the trimer-stabilized HR1 peptide. All gp41 mutations enhance 6HB stability to outcompete inhibitors, but gp120 adaptive mutations differed between these R5 and X4 viruses, providing new insights into gp120-gp41 functional interactions affecting Env refolding during HIV entry.</jats:p>","is_dataset_classified":null,"base_score":1.6094379124341003,"endowment":1.6094379124341003,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"30894471","pmcid":"PMC6532104","openalex_id":"https://openalex.org/W2923552469","authors":[],"funders":[{"funder_name":"National Natural Science Foundation of China","grant_id":"81201321","title":null},{"funder_name":"National Natural Science Foundation of China","grant_id":"81871654","title":null},{"funder_name":"HHS | U.S. Food and Drug Administration","grant_id":"","title":null}],"total_grants":3,"fwci":0.2423,"citation_percentile":0.50618087,"influential_citations":0,"citation_trend":[{"year":2019,"count":1},{"year":2020,"count":1},{"year":2024,"count":1},{"year":2025,"count":1}],"oa_status":"bronze","license":"https://journals.asm.org/non-commercial-tdm-license","oa_locations":[{"url":"https://jvi.asm.org/content/jvi/93/11/e00142-19.full.pdf","host_type":"journal"},{"url":"https://jvi.asm.org/content/jvi/93/11/e00142-19.full.pdf","host_type":"publisher"},{"url":"https://journals.asm.org/doi/pdf/10.1128/JVI.00142-19","host_type":"publisher"},{"url":"https://doi.org/10.1128/jvi.00142-19","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/30894471","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/6532104","host_type":"repository"}],"fields_of_study":["HIV Research and Treatment","Immune Cell Function and Interaction","Monoclonal and Polyclonal Antibodies Research","Anti-Retroviral Agents","Drug Resistance, Viral","Glycoproteins","HEK293 Cells","HIV Envelope Protein gp120","HIV Envelope Protein gp41","HIV Fusion Inhibitors","HIV Infections","HIV Seropositivity","HIV-1","Humans","Mutation","Protein Conformation","Receptors, CCR5","Receptors, CXCR4"],"mesh_terms":["Glycoproteins","HIV Seropositivity","Humans","Mutation","Protein Conformation","HIV-1","HIV Infections","HIV Envelope Protein gp120","HIV Envelope Protein gp41","Receptors, CCR5","Receptors, CXCR4","HIV Fusion Inhibitors","Drug Resistance, Viral","Anti-Retroviral Agents","HEK293 Cells"],"keywords":["Gp41","Heptad repeat","Biology","Lipid bilayer fusion","Virus","Viral entry","Glycoprotein","Entry inhibitor","Viral envelope","Virology","Peptide","Protein subunit","Peptide sequence","Cell biology","Viral replication","Molecular biology","Biochemistry","Genetics","Gene","Epitope","Antibody","HIV-1","Resistance","Fusion","Conformational changes","Fusion Inhibitor"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Good health and well-being"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[{"name":"gen"},{"name":"pdb"}],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-03T01:01:14.514502Z","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":[]}