ArticleProceedings of the National Academy of Sciences of the United States of America2012
Stochastic effects are important in intrahost HIV evolution even when viral loads are high.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
9 citing papers in PubMed, 18 citations in OpenAlex.
- EscaPRRS-ORF5: a structure-aware evolutionary framework for prioritizing immune escape-prone variants in porcine reproductive and respiratory syndrome virus.Bioinformatics (Oxford, England) · 2026Article
- HIV broadly neutralizing antibody escape dynamics drive the outcome of AAV-vectored immunotherapy in humanized mice.Immunity · 2026Article
- Variation of TNF modulates cellular immunity of gregarious and solitary locusts against fungal pathogenProceedings of the National Academy of Sciences of the United States of America · 2022Article
- Mathematical modeling of N-803 treatment in SIV-infected non-human primates.PLoS computational biology · 2021Article
- Towards multiscale modeling of the CD8Wiley interdisciplinary reviews. Systems biology and medicine · 2019Review
- Analysis of immune-related genes during Nora virus infection ofAIMS microbiology · 2018Article
- Solving Immunology?Trends in immunology · 2017Review
- Exploiting Bioprocessing Fluctuations to Elicit the Mechanistics of De Novo Lipogenesis in Yarrowia lipolytica.PloS one · 2017Article
- Inferring HIV Escape Rates from Multi-Locus Genotype Data.Frontiers in immunology · 2013Article
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Blood plasma viral loads and the time to progress to AIDS differ widely among untreated HIV-infected humans. Although people with certain HLA (HLA-I) alleles are more likely to control HIV infections without therapy, the majority of such untreated individuals exhibit high viral loads and progress to AIDS. Stochastic effects are considered unimportant for evolutionary dynamics in HIV-infected people when viral load is high or when selective forces strongly drive mutation. We describe a computational study of host-pathogen interaction demonstrating that stochastic effects can have a profound influence on disease dynamics, even in cases of high viral load and strong selective pressure. These stochastic effects are pronounced when the virus must traverse a fitness "barrier" in sequence space to escape the host's cytotoxic T-lymphocyte (CTL) response, as often occurs when a fitness defect imposed by a CTL-driven mutation must be compensated for by other mutations. These "barrier-crossing" events are infrequent and stochastic, resulting in divergent disease outcomes in genetically identical individuals infected by the same viral strain. Our results reveal how genetic determinants of the CTL response control the probability with which an individual is able to control HIV infection indefinitely, and thus provide clues for vaccine design.
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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.