ArticleJournal of virology2013
Frequent and variable cytotoxic-T-lymphocyte escape-associated fitness costs in the human immunodeficiency virus type 1 subtype B Gag proteins.
Article in Journal of virology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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Who cites it
37 citing papers in PubMed, 46 citations in OpenAlex.
- HLA-B*14:02-Restricted Env-Specific CD8Journal of virology · 2017Trial
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- Sustained aviremia despite anti-retroviral therapy non-adherence in male children after in utero HIV transmission.Nature medicine · 2024Article
- Subtype-specific differences in Gag-protease replication capacity of HIV-1 isolates from East and West Africa.Retrovirology · 2021Article
- Protective HLA alleles are associated with reduced LPS levels in acute HIV infection with implications for immune activation and pathogenesis.PLoS pathogens · 2019Article
- Clinical and evolutionary consequences of HIV adaptation to HLA: implications for vaccine and cure.Current opinion in HIV and AIDS · 2019Review
- HIV-1 and SIV Infection Are Associated with Early Loss of Lung Interstitial CD4+ T Cells and Dissemination of Pulmonary Tuberculosis.Cell reports · 2019Article
- High-Resolution Sequencing of Viral Populations during Early Simian Immunodeficiency Virus Infection Reveals Evolutionary Strategies for Rapid Escape from Emerging Env-Specific Antibody Responses.Journal of virology · 2018Article
- Weaker HLA Footprints on HIV in the Unique and Highly Genetically Admixed Host Population of Mexico.Journal of virology · 2018Article
- Article
- Role of HIV-specific CD8The Journal of experimental medicine · 2017Article
- In vivo virulence of MHC-adapted AIDS virus serially-passaged through MHC-mismatched hosts.PLoS pathogens · 2017Article
- HIV-1 epitopes presented by MHC class I types associated with superior immune containment of viremia have highly constrained fitness landscapes.PLoS pathogens · 2017Article
- Adaptive HIV-1 evolutionary trajectories are constrained by protein stability.Virus evolution · 2017Article
- HIV-1 immune evasion-a threat to effective vaccines?Nature medicine · 2016Article
- Article
- Consequences of HLA-B*13-Associated Escape Mutations on HIV-1 Replication and Nef Function.Journal of virology · 2015Article
- The Breadth of Expandable Memory CD8+ T Cells Inversely Correlates with Residual Viral Loads in HIV Elite Controllers.Journal of virology · 2015Article
- Global Database-Driven Assessment of HIV-1 Adaptation to the Immune Repertoires of Human Populations.Journal of virology · 2015Article
- Fitness-Balanced Escape Determines Resolution of Dynamic Founder Virus Escape Processes in HIV-1 Infection.Journal of virology · 2015Article
Corrections and comments
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Authors and funding
11 authors at 4 institutions in 3 countries.
Funding
Abstract
Cytotoxic-T-lymphocyte (CTL) escape mutations undermine the durability of effective human immunodeficiency virus type 1 (HIV-1)-specific CD8(+) T cell responses. The rate of CTL escape from a given response is largely governed by the net of all escape-associated viral fitness costs and benefits. The observation that CTL escape mutations can carry an associated fitness cost in terms of reduced virus replication capacity (RC) suggests a fitness cost-benefit trade-off that could delay CTL escape and thereby prolong CD8 response effectiveness. However, our understanding of this potential fitness trade-off is limited by the small number of CTL escape mutations for which a fitness cost has been quantified. Here, we quantified the fitness cost of the 29 most common HIV-1B Gag CTL escape mutations using an in vitro RC assay. The majority (20/29) of mutations reduced RC by more than the benchmark M184V antiretroviral drug resistance mutation, with impacts ranging from 8% to 69%. Notably, the reduction in RC was significantly greater for CTL escape mutations associated with protective HLA class I alleles than for those associated with nonprotective alleles. To speed the future evaluation of CTL escape costs, we also developed an in silico approach for inferring the relative impact of a mutation on RC based on its computed impact on protein thermodynamic stability. These data illustrate that the magnitude of CTL escape-associated fitness costs, and thus the barrier to CTL escape, varies widely even in the conserved Gag proteins and suggest that differential escape costs may contribute to the relative efficacy of CD8 responses.
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Registered trials
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.