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Historically, individuals living with subtype A viruses exhibit slower CD4 decline and progression to AIDS diagnosis. Despite this, there are few authentic infectious molecular clones (IMCs) of subtype A or AC recombinant transmitted founder (TF) viruses with which to investigate viral impacts on pathogenesis. In this study, we constructed 16 authentic subtype A1 and 4 A1C recombinant IMCs from the IAVI Rwandan Protocol C acute infection cohort and characterized these viruses phenotypically. The virus replicative capacity (RC) scores varied over 50-fold, but the natural substitution of non-consensus amino acids in the p17(MA) domain of Gag was generally linked to higher RC levels. Sensitivity to a panel of broadly neutralizing antibodies (bNAbs) showed that all but one TF was sensitive to N6, which targets the CD4 binding site, while bNAbs PG16 and PGT 128 had a similar level of potency but reduced breadth against our panel of viruses. In contrast, bNAb 10E8V4 revealed high breadth but much lower potency. This panel of well-characterized, authentic subtype A and AC recombinant IMCs provides a resource for studies on the role of the virus subtype in HIV-1 transmission, pathogenesis, and vaccine design.<\/jats:p>","DOI":"10.3390\/v16111706","type":"journal-article","created":{"date-parts":[[2024,10,31]],"date-time":"2024-10-31T06:55:37Z","timestamp":1730357737000},"page":"1706","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Phenotypic Characterization of Subtype A and Recombinant AC Transmitted\/Founder Viruses from a Rwandan HIV-1 Heterosexual Transmission Cohort"],"prefix":"10.3390","volume":"16","author":[{"given":"Ling","family":"Yue","sequence":"first","affiliation":[{"name":"Emory Vaccine Center, Emory National Primate Research Center, Atlanta, GA 30329, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rui","family":"Xu","sequence":"additional","affiliation":[{"name":"Emory Vaccine Center, Emory National Primate Research Center, Atlanta, GA 30329, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Samantha","family":"Mclnally","sequence":"additional","affiliation":[{"name":"Emory Vaccine Center, Emory National Primate Research Center, Atlanta, GA 30329, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qianhong","family":"Qin","sequence":"additional","affiliation":[{"name":"Emory Vaccine Center, Emory National Primate Research Center, Atlanta, GA 30329, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9507-4894","authenticated-orcid":false,"given":"Jake W.","family":"Rhodes","sequence":"additional","affiliation":[{"name":"Emory Vaccine Center, Emory National Primate Research Center, Atlanta, GA 30329, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Erick","family":"Muok","sequence":"additional","affiliation":[{"name":"Center for Family Health Research (Formally Project San Francisco), Kigali P.O. Box 780, Rwanda"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9841-1040","authenticated-orcid":false,"given":"Gisele","family":"Umviligihozo","sequence":"additional","affiliation":[{"name":"Center for Family Health Research (Formally Project San Francisco), Kigali P.O. Box 780, Rwanda"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kelsie","family":"Brooks","sequence":"additional","affiliation":[{"name":"Emory Vaccine Center, Emory National Primate Research Center, Atlanta, GA 30329, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiayi","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Biostatistics, Emory University, Atlanta, GA 30322, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1583-146X","authenticated-orcid":false,"given":"Zhaohui","family":"Qin","sequence":"additional","affiliation":[{"name":"Department of Biostatistics, Emory University, Atlanta, GA 30322, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jean","family":"Bizimana","sequence":"additional","affiliation":[{"name":"Center for Family Health Research (Formally Project San Francisco), Kigali P.O. Box 780, Rwanda"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jonathan","family":"Hare","sequence":"additional","affiliation":[{"name":"International AIDS Vaccine Initiative, New York, NY 10004, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Matthew A.","family":"Price","sequence":"additional","affiliation":[{"name":"International AIDS Vaccine Initiative, New York, NY 10004, USA"},{"name":"UCSF Department of Epidemiology and Biostatistics, San Francisco, CA 94158, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9150-3898","authenticated-orcid":false,"given":"Susan A.","family":"Allen","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Emory University, Atlanta, GA 30322, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9475-5436","authenticated-orcid":false,"given":"Etienne","family":"Karita","sequence":"additional","affiliation":[{"name":"Center for Family Health Research (Formally Project San Francisco), Kigali P.O. 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