ArticlePLoS computational biology2016
Conflicting Selection Pressures Will Constrain Viral Escape from Interfering Particles: Principles for Designing Resistance-Proof Antivirals.
Article in PLoS computational biology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
What it found
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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
20 citing papers in PubMed, 29 citations in OpenAlex.
- Coevolutionary dynamics of viruses and their defective interfering particles.PLoS computational biology · 2026Article
- Coevolutionary dynamics of viruses and their defective interfering particles.bioRxiv : the preprint server for biology · 2025Article
- Tradeoffs between proliferation and transmission in virus evolution- insights from evolutionary and functional analyses of SARS-CoV-2.Virology journal · 2025Article
- Review
- Navigating a Fine Balance: Point-Mutant Cheater Viruses Disrupt the Viral Replication Cycle.Molecular biology and evolution · 2025Article
- Engineered deletions of HIV replicate conditionally to reduce disease in nonhuman primates.Science (New York, N.Y.) · 2024Article
- Shared sequence characteristics identified in non-canonical rearrangements of HSV-1 genomes.Journal of virology · 2023Article
- Evolutionary implications of SARS-CoV-2 vaccination for the future design of vaccination strategies.Communications medicine · 2023Review
- Evolutionary dynamics within and among competing groups.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- The conditional defector strategies can violate the most crucial supporting mechanisms of cooperation.Scientific reports · 2022Article
- Therapeutic interfering particles exploiting viral replication and assembly mechanisms show promising performance: a modelling study.Scientific reports · 2021Article
- Article
- An evolution-based high-fidelity method of epistasis measurement: Theory and application to influenza.PLoS pathogens · 2021Article
- The evolutionary origin of the universal distribution of mutation fitness effect.PLoS computational biology · 2021Article
- Article
- Competition between social cheater viruses is driven by mechanistically different cheating strategies.Science advances · 2020Article
- Defective viral genomes are key drivers of the virus-host interaction.Nature microbiology · 2019Review
- Predicting HIV-1 transmission and antibody neutralization efficacy in vivo from stoichiometric parameters.PLoS pathogens · 2017Article
- Article
- Exploiting Genetic Interference for Antiviral Therapy.PLoS genetics · 2016Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
The rapid evolution of RNA-encoded viruses such as HIV presents a major barrier to infectious disease control using conventional pharmaceuticals and vaccines. Previously, it was proposed that defective interfering particles could be developed to indefinitely control the HIV/AIDS pandemic; in individual patients, these engineered molecular parasites were further predicted to be refractory to HIV's mutational escape (i.e., be 'resistance-proof'). However, an outstanding question has been whether these engineered interfering particles-termed Therapeutic Interfering Particles (TIPs)-would remain resistance-proof at the population-scale, where TIP-resistant HIV mutants may transmit more efficiently by reaching higher viral loads in the TIP-treated subpopulation. Here, we develop a multi-scale model to test whether TIPs will maintain indefinite control of HIV at the population-scale, as HIV ('unilaterally') evolves toward TIP resistance by limiting the production of viral proteins available for TIPs to parasitize. Model results capture the existence of two intrinsic evolutionary tradeoffs that collectively prevent the spread of TIP-resistant HIV mutants in a population. First, despite their increased transmission rates in TIP-treated sub-populations, unilateral TIP-resistant mutants are shown to have reduced transmission rates in TIP-untreated sub-populations. Second, these TIP-resistant mutants are shown to have reduced growth rates (i.e., replicative fitness) in both TIP-treated and TIP-untreated individuals. As a result of these tradeoffs, the model finds that TIP-susceptible HIV strains continually outcompete TIP-resistant HIV mutants at both patient and population scales when TIPs are engineered to express >3-fold more genomic RNA than HIV expresses. Thus, the results provide design constraints for engineering population-scale therapies that may be refractory to the acquisition of antiviral resistance.
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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.