Hanna B. ScintoSandeep GuptaSwati ThoratMuhammad M. MukhtarAnthony GriffithsJennifer DelgadoElizabeth PlakeHemant K. VyasAmanda StricklandSiddappa N. ByrareddyDavid C. MontefioriCelia LaBrancheRanajit PalJim TreeceSharon OrndorffMaria Grazia FerrariDeborah WeissAgnes Laurence ChenineRobert McLindenNelson MichaelJerome H. KimMerlin L. RobbSupachai Rerks-NgarmPunnee PitisuttithumSorachai NitayaphanRuth M. RuprechtDuke University Medical CenterAdvanced BioScience Laboratories, Inc.International Vaccine Institute, SeoulTexas Biomedical Research InstituteUniversity of Texas Health Science Center at San AntonioUniversity of Nebraska Medical CenterArmed Forces Research Institute of Medical Sciences, ThailandThailand Ministry of Public HealthHJFDana-Farber Cancer InstituteMahidol UniversityHarvard Medical School2019-08-232019-08-232018-07-01Journal of Virology. Vol.92, No.14 (2018)109855140022538X2-s2.0-85049202181https://repository.li.mahidol.ac.th/handle/123456789/44732©2018 American Society for Microbiology. The phase III RV144 human immunodeficiency virus (HIV) vaccine trial conducted in Thailand remains the only study to show efficacy in decreasing the HIV acquisition risk. In Thailand, circulating recombinant forms of HIV clade A/E (CRF01_AE) predominate; in such viruses, env originates from clade E (HIV-E). We constructed a simian-human immunodeficiency virus (SHIV) chimera carrying env isolated from an RV144 placebo recipient in the SHIV-1157ipd3N4 backbone. The latter contains long terminal repeats (LTRs) with duplicated NF-B sites, thus resembling HIV LTRs. We devised a novel strategy to adapt the parental infectious molecular clone (IMC), R5 SHIV-E1, to rhesus macaques: the simultaneous depletion of B and CD8 cells followed by the intramuscular inoculation of proviral DNA and repeated administrations of cell-free virus. High-level viremia and CD4 T-cell depletion ensued. Passage 3 virus unexpectedly caused acute, irreversible CD4 T-cell loss; the partially adapted SHIV had become dual tropic. Virus and IMCs with exclusive R5 tropism were reisolated from earlier passages, combined, and used to complete adaptation through additional macaques. The final isolate, SHIV-E1p5, remained solely R5 tropic. It had a tier 2 neutralization phenotype, was mucosally transmissible, and was pathogenic. Deep sequencing revealed 99% Env amino acid sequence conservation; X4-only and dual-tropic strains had evolved independently from an early branch of parental SHIV-E1. To conclude, our primate model data reveal that SHIV-E1p5 recapitulates important aspects of HIV transmission and pathobiology in humans.Mahidol UniversityAgricultural and Biological SciencesImmunology and MicrobiologyArticleSCOPUS10.1128/JVI.02222-17