{"doi":"10.1128/jvi.02741-09","title":"Autologous Neutralizing Antibodies to the Transmitted/Founder Viruses Emerge Late after Simian Immunodeficiency Virus SIVmac251 Infection of Rhesus Monkeys","abstract":"<jats:title>ABSTRACT</jats:title>\n          <jats:p>\n            While the simian immunodeficiency virus (SIV)-infected rhesus monkey is an important animal model for human immunodeficiency virus type 1 (HIV-1) infection of humans, much remains to be learned about the evolution of the humoral immune response in this model. In HIV-1 infection, autologous neutralizing antibodies emerge 2 to 3 months after infection. However, the ontogeny of the SIV-specific neutralizing antibody response in mucosally infected animals has not been defined. We characterized the kinetics of the autologous neutralizing antibody response to the transmitted/founder SIVmac251 using a pseudovirion-based TZM-bl cell assay and monitored\n            <jats:italic>env</jats:italic>\n            sequence evolution using single-genome amplification in four rhesus animals that were infected via intrarectal inoculations. We show that the SIVmac251 founder viruses induced neutralizing antibodies at 5 to 8 months after infection. Despite their slow emergence and low titers, these neutralizing antibodies selected for escape mutants that harbored substitutions and deletions in variable region 1 (V1), V2, and V4 of Env. The neutralizing antibody response was initially focused on V4 at 5 to 8 months after infection and then targeted V1/V2 and V4 by 16 months. These findings reveal a striking delay in the development of neutralizing antibodies in SIVmac-infected animals, thus raising questions concerning the suitability of SIVmac251 as a challenge strain to screen AIDS vaccines that elicit neutralizing antibodies as a means to prevent virus acquisition. They also illustrate the capacity of the SIVmac quasispecies to modify antigenic determinants in response to very modest titers of neutralizing antibodies.\n          </jats:p>","journal":"Journal of Virology","year":2010,"id":590026,"datarank":1.1676570496507934,"base_score":3.58351893845611,"endowment":3.58351893845611,"self_citation_contribution":0.5375278407684165,"citation_network_contribution":0.6301292088823768,"self_endowment_contribution":0.5375278407684165,"citer_contribution":0.6301292088823768,"corpus_percentile":null,"corpus_rank":null,"citation_count":35,"citer_count":25,"citers_with_citation_signal":21,"citers_with_endowment":21,"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":1509663,"name":"Ishita Rahman","orcid":null,"position":1,"is_corresponding":false},{"id":280550,"name":"Peter Hraber","orcid":"0000-0002-2920-4897","position":2,"is_corresponding":false},{"id":1509664,"name":"Rory T. Coffey","orcid":null,"position":3,"is_corresponding":false},{"id":1509665,"name":"Daiva Nevidomskyte","orcid":null,"position":4,"is_corresponding":false},{"id":55293,"name":"Ayush Giri","orcid":"0000-0002-7786-4670","position":5,"is_corresponding":false},{"id":795416,"name":"Mohammed Asmal","orcid":"0009-0002-9834-1286","position":6,"is_corresponding":false},{"id":1509666,"name":"Svetlana Miljkovic","orcid":null,"position":7,"is_corresponding":false},{"id":545084,"name":"Marcus Daniels","orcid":null,"position":8,"is_corresponding":false},{"id":384637,"name":"James B. Whitney","orcid":"0000-0003-3674-0193","position":9,"is_corresponding":false},{"id":233486,"name":"Brandon F. Keele","orcid":"0000-0002-2381-1151","position":10,"is_corresponding":false},{"id":91120,"name":"Beatrice H. Hahn","orcid":"0000-0002-9400-9887","position":11,"is_corresponding":false},{"id":138597,"name":"Bette T. Korber","orcid":null,"position":12,"is_corresponding":false},{"id":253820,"name":"George M. Shaw","orcid":"0000-0002-2338-4532","position":13,"is_corresponding":false},{"id":16991,"name":"Michael S. Seaman","orcid":"0000-0001-6444-3562","position":14,"is_corresponding":false},{"id":611232,"name":"Norman L. Letvin","orcid":null,"position":15,"is_corresponding":false},{"id":1258374,"name":"Wendy W. Yeh","orcid":"0000-0002-8026-1344","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Autologous Neutralizing Antibodies to the Transmitted/Founder Viruses Emerge Late after Simian Immunodeficiency Virus SIVmac251 Infection of Rhesus Monkeys","abstract":"<jats:title>ABSTRACT</jats:title>\n          <jats:p>\n            While the simian immunodeficiency virus (SIV)-infected rhesus monkey is an important animal model for human immunodeficiency virus type 1 (HIV-1) infection of humans, much remains to be learned about the evolution of the humoral immune response in this model. In HIV-1 infection, autologous neutralizing antibodies emerge 2 to 3 months after infection. However, the ontogeny of the SIV-specific neutralizing antibody response in mucosally infected animals has not been defined. We characterized the kinetics of the autologous neutralizing antibody response to the transmitted/founder SIVmac251 using a pseudovirion-based TZM-bl cell assay and monitored\n            <jats:italic>env</jats:italic>\n            sequence evolution using single-genome amplification in four rhesus animals that were infected via intrarectal inoculations. We show that the SIVmac251 founder viruses induced neutralizing antibodies at 5 to 8 months after infection. Despite their slow emergence and low titers, these neutralizing antibodies selected for escape mutants that harbored substitutions and deletions in variable region 1 (V1), V2, and V4 of Env. The neutralizing antibody response was initially focused on V4 at 5 to 8 months after infection and then targeted V1/V2 and V4 by 16 months. These findings reveal a striking delay in the development of neutralizing antibodies in SIVmac-infected animals, thus raising questions concerning the suitability of SIVmac251 as a challenge strain to screen AIDS vaccines that elicit neutralizing antibodies as a means to prevent virus acquisition. They also illustrate the capacity of the SIVmac quasispecies to modify antigenic determinants in response to very modest titers of neutralizing antibodies.\n          </jats:p>","is_dataset_classified":null,"base_score":3.58351893845611,"endowment":3.58351893845611,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"20357097","pmcid":"PMC2876635","openalex_id":"https://openalex.org/W2016548274","authors":[],"funders":[{"funder_name":"NIAID NIH HHS","grant_id":"K08-AI069995","title":null},{"funder_name":"NIAID NIH HHS","grant_id":"U01 AI067854","title":null},{"funder_name":"NIAID NIH HHS","grant_id":"AI067854","title":null},{"funder_name":"NIAID NIH HHS","grant_id":"R33 AI087383","title":null},{"funder_name":"NIAID NIH HHS","grant_id":"T32 AI007387","title":null},{"funder_name":"NIAID NIH HHS","grant_id":"U19 AI067854","title":null},{"funder_name":"NIAID NIH HHS","grant_id":"AI087383","title":null},{"funder_name":"NIAID NIH HHS","grant_id":"K08 AI069995","title":null},{"funder_name":"NIAID NIH HHS","grant_id":"R21 AI087383","title":null}],"total_grants":9,"fwci":1.6889,"citation_percentile":0.82008368,"influential_citations":0,"citation_trend":[{"year":2012,"count":6},{"year":2013,"count":3},{"year":2014,"count":3},{"year":2015,"count":4},{"year":2016,"count":1},{"year":2017,"count":3},{"year":2018,"count":2},{"year":2020,"count":2},{"year":2021,"count":1},{"year":2022,"count":1},{"year":2023,"count":1},{"year":2025,"count":1}],"oa_status":"closed","license":"https://journals.asm.org/non-commercial-tdm-license","oa_locations":[{"url":"https://journals.asm.org/doi/pdf/10.1128/JVI.02741-09","host_type":"publisher"},{"url":"https://doi.org/10.1128/jvi.02741-09","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/20357097","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/2876635","host_type":"repository"}],"fields_of_study":["HIV Research and Treatment","Immune Cell Function and Interaction","HIV/AIDS drug development and treatment"],"mesh_terms":["Amino Acid Sequence","Animals","Antibodies, Viral","Disease Models, Animal","Humans","Macaca mulatta","Molecular Sequence Data","Phylogeny","Viral Envelope Proteins","Simian Immunodeficiency Virus","HIV-1","HIV Infections","Simian Acquired Immunodeficiency Syndrome","Sequence Alignment","Antibodies, Neutralizing","Simian immunodeficiency virus"],"keywords":["Virology","Simian immunodeficiency virus","Biology","Neutralizing antibody","Viral quasispecies","Antibody","Virus","Simian","Immune system","Titer","Immunology"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Good health and well-being"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[{"name":"gen"}],"source":"live","citation_network_status":"fetched"},"created_at":"2026-07-24T12:28:04.978959Z","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":[]}