Phenotypic Characterization of Subtype A and Recombinant AC Transmitted/Founder Viruses from a Rwandan HIV-1 Heterosexual Transmission Cohort
HIV-1 subtypes have distinct geographical distributions, with subtypes A, C, and D and inter-subtype recombinants circulating in sub-Saharan Africa. Historically, individuals living with subtype A viruses exhibit slower CD4 decline and progression to AIDS diagnosis. Despite this, there are few authe...
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2024-10-01
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| author | Ling Yue Rui Xu Samantha Mclnally Qianhong Qin Jake W. Rhodes Erick Muok Gisele Umviligihozo Kelsie Brooks Jiayi Zhang Zhaohui Qin Jean Bizimana Jonathan Hare Matthew A. Price Susan A. Allen Etienne Karita Eric Hunter |
| author_facet | Ling Yue Rui Xu Samantha Mclnally Qianhong Qin Jake W. Rhodes Erick Muok Gisele Umviligihozo Kelsie Brooks Jiayi Zhang Zhaohui Qin Jean Bizimana Jonathan Hare Matthew A. Price Susan A. Allen Etienne Karita Eric Hunter |
| author_sort | Ling Yue |
| collection | DOAJ |
| description | HIV-1 subtypes have distinct geographical distributions, with subtypes A, C, and D and inter-subtype recombinants circulating in sub-Saharan Africa. 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. |
| format | Article |
| id | doaj-art-e08124aee663449db461dbfda7e63337 |
| institution | OA Journals |
| issn | 1999-4915 |
| language | English |
| publishDate | 2024-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Viruses |
| spelling | doaj-art-e08124aee663449db461dbfda7e633372025-08-20T01:54:04ZengMDPI AGViruses1999-49152024-10-011611170610.3390/v16111706Phenotypic Characterization of Subtype A and Recombinant AC Transmitted/Founder Viruses from a Rwandan HIV-1 Heterosexual Transmission CohortLing Yue0Rui Xu1Samantha Mclnally2Qianhong Qin3Jake W. Rhodes4Erick Muok5Gisele Umviligihozo6Kelsie Brooks7Jiayi Zhang8Zhaohui Qin9Jean Bizimana10Jonathan Hare11Matthew A. Price12Susan A. Allen13Etienne Karita14Eric Hunter15Emory Vaccine Center, Emory National Primate Research Center, Atlanta, GA 30329, USAEmory Vaccine Center, Emory National Primate Research Center, Atlanta, GA 30329, USAEmory Vaccine Center, Emory National Primate Research Center, Atlanta, GA 30329, USAEmory Vaccine Center, Emory National Primate Research Center, Atlanta, GA 30329, USAEmory Vaccine Center, Emory National Primate Research Center, Atlanta, GA 30329, USACenter for Family Health Research (Formally Project San Francisco), Kigali P.O. Box 780, RwandaCenter for Family Health Research (Formally Project San Francisco), Kigali P.O. Box 780, RwandaEmory Vaccine Center, Emory National Primate Research Center, Atlanta, GA 30329, USADepartment of Biostatistics, Emory University, Atlanta, GA 30322, USADepartment of Biostatistics, Emory University, Atlanta, GA 30322, USACenter for Family Health Research (Formally Project San Francisco), Kigali P.O. Box 780, RwandaInternational AIDS Vaccine Initiative, New York, NY 10004, USAInternational AIDS Vaccine Initiative, New York, NY 10004, USADepartment of Pathology and Laboratory Medicine, Emory University, Atlanta, GA 30322, USACenter for Family Health Research (Formally Project San Francisco), Kigali P.O. Box 780, RwandaEmory Vaccine Center, Emory National Primate Research Center, Atlanta, GA 30329, USAHIV-1 subtypes have distinct geographical distributions, with subtypes A, C, and D and inter-subtype recombinants circulating in sub-Saharan Africa. 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.https://www.mdpi.com/1999-4915/16/11/1706infectious molecular cloneIMCvirus replicative capacityco-receptor usagebNAb potency and breadth |
| spellingShingle | Ling Yue Rui Xu Samantha Mclnally Qianhong Qin Jake W. Rhodes Erick Muok Gisele Umviligihozo Kelsie Brooks Jiayi Zhang Zhaohui Qin Jean Bizimana Jonathan Hare Matthew A. Price Susan A. Allen Etienne Karita Eric Hunter Phenotypic Characterization of Subtype A and Recombinant AC Transmitted/Founder Viruses from a Rwandan HIV-1 Heterosexual Transmission Cohort Viruses infectious molecular clone IMC virus replicative capacity co-receptor usage bNAb potency and breadth |
| title | Phenotypic Characterization of Subtype A and Recombinant AC Transmitted/Founder Viruses from a Rwandan HIV-1 Heterosexual Transmission Cohort |
| title_full | Phenotypic Characterization of Subtype A and Recombinant AC Transmitted/Founder Viruses from a Rwandan HIV-1 Heterosexual Transmission Cohort |
| title_fullStr | Phenotypic Characterization of Subtype A and Recombinant AC Transmitted/Founder Viruses from a Rwandan HIV-1 Heterosexual Transmission Cohort |
| title_full_unstemmed | Phenotypic Characterization of Subtype A and Recombinant AC Transmitted/Founder Viruses from a Rwandan HIV-1 Heterosexual Transmission Cohort |
| title_short | Phenotypic Characterization of Subtype A and Recombinant AC Transmitted/Founder Viruses from a Rwandan HIV-1 Heterosexual Transmission Cohort |
| title_sort | phenotypic characterization of subtype a and recombinant ac transmitted founder viruses from a rwandan hiv 1 heterosexual transmission cohort |
| topic | infectious molecular clone IMC virus replicative capacity co-receptor usage bNAb potency and breadth |
| url | https://www.mdpi.com/1999-4915/16/11/1706 |
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