Trial reportPLoS pathogens2012
Role of transmitted Gag CTL polymorphisms in defining replicative capacity and early HIV-1 pathogenesis.
Trial report in PLoS pathogens, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 73 papers.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
73 citing papers in PubMed.
- Trial
- Capsid-Targeting Biologic Achieves Broad HIV-1 Neutralization with a High Barrier to Resistance.International journal of molecular sciences · 2026Article
- Attenuation of HIV severity by slightly deleterious mutations can explain the long-term trajectory of virulence evolution.PLoS computational biology · 2025Article
- Comparison of viral phenotype and inflammatory biomarker responses in acute HIV-1 subtype A and C infections.Frontiers in microbiology · 2025Article
- Article
- Higher HIV-1 evolutionary rate is associated with cytotoxic T lymphocyte escape mutations in infants.Journal of virology · 2024Article
- Insights to HIV-1 coreceptor usage by estimating HLA adaptation with Bayesian generalized linear mixed models.PLoS computational biology · 2023Article
- Article
- Role of Early Life Cytotoxic T Lymphocyte and Natural Killer Cell Immunity in Paediatric HIV Cure/Remission in the Anti-Retroviral Therapy Era.Frontiers in immunology · 2022Review
- Subtype-specific differences in Gag-protease replication capacity of HIV-1 isolates from East and West Africa.Retrovirology · 2021Article
- Article
- Cohort Profile: IAVI's HIV epidemiology and early infection cohort studies in Africa to support vaccine discovery.International journal of epidemiology · 2021Article
- HIV-1Viruses · 2021Article
- Dual CD4-based CAR T cells with distinct costimulatory domains mitigate HIV pathogenesis in vivo.Nature medicine · 2020Article
- Infection with multiple HIV-1 founder variants is associated with lower viral replicative capacity, faster CD4+ T cell decline and increased immune activation during acute infection.PLoS pathogens · 2020Article
- Impact of HLA-B*52:01-Driven Escape Mutations on Viral Replicative Capacity.Journal of virology · 2020Article
- Accumulated mutations by 6 months of infection collectively render transmitted/founder HIV-1 significantly less fit.The Journal of infection · 2020Article
- Protective HLA alleles are associated with reduced LPS levels in acute HIV infection with implications for immune activation and pathogenesis.PLoS pathogens · 2019Article
- Delayed disease progression in HIV-2: the importance of TRIM5α and the retroviral capsid.Clinical and experimental immunology · 2019Review
- Clinical and evolutionary consequences of HIV adaptation to HLA: implications for vaccine and cure.Current opinion in HIV and AIDS · 2019Review
13 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
21 authors.
Funding
Abstract
Initial studies of 88 transmission pairs in the Zambia Emory HIV Research Project cohort demonstrated that the number of transmitted HLA-B associated polymorphisms in Gag, but not Nef, was negatively correlated to set point viral load (VL) in the newly infected partners. These results suggested that accumulation of CTL escape mutations in Gag might attenuate viral replication and provide a clinical benefit during early stages of infection. Using a novel approach, we have cloned gag sequences isolated from the earliest seroconversion plasma sample from the acutely infected recipient of 149 epidemiologically linked Zambian transmission pairs into a primary isolate, subtype C proviral vector, MJ4. We determined the replicative capacity (RC) of these Gag-MJ4 chimeras by infecting the GXR25 cell line and quantifying virion production in supernatants via a radiolabeled reverse transcriptase assay. We observed a statistically significant positive correlation between RC conferred by the transmitted Gag sequence and set point VL in newly infected individuals (p = 0.02). Furthermore, the RC of Gag-MJ4 chimeras also correlated with the VL of chronically infected donors near the estimated date of infection (p = 0.01), demonstrating that virus replication contributes to VL in both acute and chronic infection. These studies also allowed for the elucidation of novel sites in Gag associated with changes in RC, where rare mutations had the greatest effect on fitness. Although we observed both advantageous and deleterious rare mutations, the latter could point to vulnerable targets in the HIV-1 genome. Importantly, RC correlated significantly (p = 0.029) with the rate of CD4+ T cell decline over the first 3 years of infection in a manner that is partially independent of VL, suggesting that the replication capacity of HIV-1 during the earliest stages of infection is a determinant of pathogenesis beyond what might be expected based on set point VL alone.
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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.