{"doi":"10.17615/b379-9591","title":"High Multiplicity Infection by HIV-1 in Men Who Have Sex with Men","abstract":"Elucidating virus-host interactions responsible for HIV-1 transmission is important for advancing HIV-1 prevention strategies. To this end, single genome amplification (SGA) and sequencing of HIV-1 within the context of a model of random virus evolution has made possible for the first time an unambiguous identification of transmitted/founder viruses and a precise estimation of their numbers. Here, we applied this approach to HIV-1 env analyses in a cohort of acutely infected men who have sex with men (MSM) and found that a high proportion (10 of 28; 36%) had been productively infected by more than one virus. In subjects with multivariant transmission, the minimum number of transmitted viruses ranged from 2 to 10 with viral recombination leading to rapid and extensive genetic shuffling among virus lineages. A combined analysis of these results, together with recently published findings based on identical SGA methods in largely heterosexual (HSX) cohorts, revealed a significantly higher frequency of multivariant transmission in MSM than in HSX [19 of 50 subjects (38%) versus 34 of 175 subjects (19%); Fisher's exact p = 0.008]. To further evaluate the SGA strategy for identifying transmitted/founder viruses, we analyzed 239 overlapping 5′ and 3′ half genome or env-only sequences from plasma viral RNA (vRNA) and blood mononuclear cell DNA in an MSM subject who had a particularly well-documented virus exposure history 3–6 days before symptom onset and 14–17 days before peak plasma viremia (47,600,000 vRNA molecules/ml). All 239 sequences coalesced to a single transmitted/founder virus genome in a time frame consistent with the clinical history, and a molecular clone of this genome encoded replication competent virus in accord with model predictions. Higher multiplicity of HIV-1 infection in MSM compared with HSX is consistent with the demonstrably higher epidemiological risk of virus acquisition in MSM and could indicate a greater challenge for HIV-1 vaccines than previously recognized.","journal":"UNC Libraries","year":2020,"id":109834,"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":8,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.958,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":253820,"name":"George M. Shaw","orcid":"0000-0002-2338-4532","position":1,"is_corresponding":false},{"id":291274,"name":"Alan S. Perelson","orcid":"0000-0002-2455-0002","position":2,"is_corresponding":false},{"id":524563,"name":"Julie M. Decker","orcid":null,"position":3,"is_corresponding":false},{"id":24197,"name":"Bette Korber","orcid":"0000-0002-2026-5757","position":4,"is_corresponding":false},{"id":103727,"name":"Elena Giorgi","orcid":"0000-0003-2968-1033","position":5,"is_corresponding":false},{"id":249712,"name":"Myron S. Cohen","orcid":"0000-0001-5917-9664","position":6,"is_corresponding":false},{"id":233486,"name":"Brandon F. Keele","orcid":"0000-0002-2381-1151","position":7,"is_corresponding":false},{"id":91120,"name":"Beatrice H. Hahn","orcid":"0000-0002-9400-9887","position":8,"is_corresponding":false},{"id":524564,"name":"Martin Markowitz","orcid":null,"position":9,"is_corresponding":false},{"id":325082,"name":"Jesus F. Salazar-Gonzalez","orcid":"0000-0003-4626-6448","position":10,"is_corresponding":false},{"id":524565,"name":"Charles B. Hicks","orcid":null,"position":11,"is_corresponding":false},{"id":103728,"name":"Tanmoy Bhattacharya","orcid":"0000-0002-1060-652X","position":12,"is_corresponding":false},{"id":434505,"name":"Charity J. Morgan","orcid":"0000-0003-0693-4739","position":13,"is_corresponding":false},{"id":524566,"name":"Joseph E. Schumacher","orcid":null,"position":14,"is_corresponding":false},{"id":523777,"name":"Maria G. Salazar","orcid":"0000-0003-0823-7697","position":15,"is_corresponding":false},{"id":280546,"name":"Shuyi Wang","orcid":"0000-0001-6831-9323","position":16,"is_corresponding":false},{"id":523778,"name":"Hui Li","orcid":"0000-0003-2600-4838","position":17,"is_corresponding":false},{"id":96347,"name":"Barton F. Haynes","orcid":"0000-0002-7643-9023","position":18,"is_corresponding":false},{"id":523779,"name":"Gerald H. Learn","orcid":"0000-0003-0434-7733","position":19,"is_corresponding":false},{"id":524567,"name":"Chuanxi Sun","orcid":null,"position":20,"is_corresponding":false},{"id":263024,"name":"Katharine J. Bar","orcid":"0000-0002-9773-0071","position":21,"is_corresponding":false},{"id":249713,"name":"Joseph J. Eron","orcid":"0000-0002-4938-0644","position":22,"is_corresponding":false},{"id":524568,"name":"Yalu Chen","orcid":null,"position":23,"is_corresponding":false},{"id":280550,"name":"Peter Hraber","orcid":"0000-0002-2920-4897","position":0,"is_corresponding":true}],"reference_count":0,"raw_metadata":null,"created_at":"2026-07-18T23:12:54.309019Z","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":[]}