ArticleProceedings of the National Academy of Sciences of the United States of America2019
A dynamical motif comprising the interactions between antigens and CD8 T cells may underlie the outcomes of viral infections.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
24 citing papers in PubMed, 52 citations in OpenAlex.
- Clinical trial simulation of antiviral drugs.Journal of virology · 2026Review
- How and why does aging occur? Updating evolutionary theory to meet a new era of data.Evolution, medicine, and public health · 2026Article
- Re-imagining T-cell receptor signaling: parallel paths may be key to discriminatory power.Journal of biosciences · 2026Article
- Bistability between acute and chronic states in a Model of Hepatitis B Virus Dynamics.Mathematical biosciences · 2025Article
- Dynamical model and geometric insights in the discontinuity theory of immunity.bioRxiv : the preprint server for biology · 2025Article
- Trade-off between the antiviral and vaccinal effects of antibody therapy in the humoral response to HIV.Journal of the Royal Society, Interface · 2024Article
- Antiviral capacity of the early CD8 T-cell response is predictive of natural control of SIV infection: Learning in vivo dynamics using ex vivo data.PLoS computational biology · 2024Article
- Modelling HIV-1 control and remission.NPJ systems biology and applications · 2024Review
- Understanding early HIV-1 rebound dynamics following antiretroviral therapy interruption: The importance of effector cell expansion.PLoS pathogens · 2024Article
- Understanding early HIV-1 rebound dynamics following antiretroviral therapy interruption: The importance of effector cell expansion.bioRxiv : the preprint server for biology · 2024Article
- Dynamical modelling of viral infection and cooperative immune protection in COVID-19 patients.PLoS computational biology · 2023Article
- Relationship between the inclusion/exclusion criteria and sample size in randomized controlled trials for SARS-CoV-2 entry inhibitors.Journal of theoretical biology · 2023Article
- Epigenetic perspectives of COVID-19: Virus infection to disease progression and therapeutic control.Biochimica et biophysica acta. Molecular basis of disease · 2022Article
- Article
- CD8Frontiers in immunology · 2022Review
- Dynamically linking influenza virus infection kinetics, lung injury, inflammation, and disease severity.eLife · 2021Article
- COVID-19 virtual patient cohort suggests immune mechanisms driving disease outcomes.PLoS pathogens · 2021Article
- Mechanistic Modeling of SARS-CoV-2 and Other Infectious Diseases and the Effects of Therapeutics.Clinical pharmacology and therapeutics · 2021Review
- A quantitative model used to compare within-host SARS-CoV-2, MERS-CoV, and SARS-CoV dynamics provides insights into the pathogenesis and treatment of SARS-CoV-2.PLoS biology · 2021Article
- Early events in hepatitis B infection: the role of inoculum dose.Proceedings. Biological sciences · 2021Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors at 2 institutions in 2 countries.
Funding
Abstract
Some viral infections culminate in very different outcomes in different individuals. They can be rapidly cleared in some, cause persistent infection in others, and cause mortality from immunopathology in yet others. The conventional view is that the different outcomes arise as a consequence of the complex interactions between a large number of different factors (virus, different immune cells, and cytokines). Here, we identify a simple dynamical motif comprising the essential interactions between antigens and CD8 T cells and posit it as predominantly determining the outcomes. Viral antigen can activate CD8 T cells, which in turn, can kill infected cells. Sustained antigen stimulation, however, can cause CD8 T-cell exhaustion, compromising effector function. Using mathematical modeling, we show that the motif comprising these interactions recapitulates all of the outcomes observed. The motif presents a conceptual framework to understand the variable outcomes of infection. It also explains a number of confounding experimental observations, including the variation in outcomes with the viral inoculum size, the evolutionary advantage of exhaustion in preventing lethal pathology, the ability of natural killer (NK) cells to act as rheostats tuning outcomes, and the role of the innate immune response in the spontaneous clearance of hepatitis C. Interventions that modulate the interactions in the motif may present routes to clear persistent infections or limit immunopathology.
Indexed as
Identifiers
What OpenQuestion holds
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.