ArticlePLoS pathogens2023
Adaptation of a transmitted/founder simian-human immunodeficiency virus for enhanced replication in rhesus macaques.
Article in PLoS pathogens, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
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Who cites it
6 citing papers in PubMed, 10 citations in OpenAlex.
- Extended hinge length of human IgG3-like antibody enhances early antiviral activity of VRC01 in SHIV-infected rhesus macaques.Journal of virology · 2026Article
- Engraftment of gene-edited hematopoietic stem cells after antibody-drug conjugate conditioning in nonhuman primates.Blood advances · 2026Article
- SHIV.D Infection Alters Production and Protein Composition of Myeloid-Derived Extracellular Vesicles.International journal of molecular sciences · 2026Article
- Article
- Identifying correlates of viral rebound timing and viral control in SHIV-infected infant macaques after ART interruption.Science translational medicine · 2025Article
- Structural and genetic basis of HIV-1 envelope V2 apex recognition by rhesus broadly neutralizing antibodies.The Journal of experimental medicine · 2025Article
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Authors and funding
17 authors at 6 institutions in 2 countries.
Funding
Abstract
Transmitted/founder (TF) simian-human immunodeficiency viruses (SHIVs) express HIV-1 envelopes modified at position 375 to efficiently infect rhesus macaques while preserving authentic HIV-1 Env biology. SHIV.C.CH505 is an extensively characterized virus encoding the TF HIV-1 Env CH505 mutated at position 375 shown to recapitulate key features of HIV-1 immunobiology, including CCR5-tropism, a tier 2 neutralization profile, reproducible early viral kinetics, and authentic immune responses. SHIV.C.CH505 is used frequently in nonhuman primate studies of HIV, but viral loads after months of infection are variable and typically lower than those in people living with HIV. We hypothesized that additional mutations besides Δ375 might further enhance virus fitness without compromising essential components of CH505 Env biology. From sequence analysis of SHIV.C.CH505-infected macaques across multiple experiments, we identified a signature of envelope mutations associated with higher viremia. We then used short-term in vivo mutational selection and competition to identify a minimally adapted SHIV.C.CH505 with just five amino acid changes that substantially improve virus replication fitness in macaques. Next, we validated the performance of the adapted SHIV in vitro and in vivo and identified the mechanistic contributions of selected mutations. In vitro, the adapted SHIV shows improved virus entry, enhanced replication on primary rhesus cells, and preserved neutralization profiles. In vivo, the minimally adapted virus rapidly outcompetes the parental SHIV with an estimated growth advantage of 0.14 days-1 and persists through suppressive antiretroviral therapy to rebound at treatment interruption. Here, we report the successful generation of a well-characterized, minimally adapted virus, termed SHIV.C.CH505.v2, with enhanced replication fitness and preserved native Env properties that can serve as a new reagent for NHP studies of HIV-1 transmission, pathogenesis, and cure.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.