Evidence map›Paper›PMID 40465541›Full record

ArticlePLoS computational biology2025

A detailed kinetic model of Eastern equine encephalitis virus replication in a susceptible host cell.

Caroline I Larkin, Matthew D Dunn, Jason E Shoemaker, William B Klimstra, James R Faeder

Abstract read
In one paragraph

Article in PLoS computational biology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

2 citing papers in PubMed.

  1. Article
  2. Systems Virology at Scale.Current opinion in systems biology · 2025
    Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

5 authors.

Caroline I LarkinJoint Carnegie Mellon University - University of Pittsburgh PhD Program in Computational Biology, Pittsburgh, Pennsylvania, United States of America.ORCID 0000-0002-0206-277X
Matthew D DunnCenter for Vaccine Research, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America.
Jason E ShoemakerDepartment of Computational and Systems Biology, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America.ORCID 0000-0003-3315-7103
William B KlimstraCenter for Vaccine Research, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America.ORCID 0000-0003-4506-7842
James R FaederDepartment of Computational and Systems Biology, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America.ORCID 0000-0001-8127-609X

Funding

Practices CoreUC7AI180311 · NIAID · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI William Paul Duprex · 2023 to 2026
$13.2M
WESTPA: A high-performance framework for simulating at the frontiers of biologyR01GM115805 · NIGMS · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI LILLIAN T CHONG · 2015 to 2026
$4.0M
An Informed Approach to Live Attenuated Vaccines against Encephalitis AlphavirusesR01AI153209 · NIAID · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI KLIMSTRA, WILLIAM B · 2020 to 2024
$2.9M
Viral and host factors in neuroinvasion of encephalitis alphavirusesR01AI160188 · NIAID · WASHINGTON UNIVERSITY · PI WILLIAM B KLIMSTRA, Robyn S. Klein · 2022 to 2026
$2.8M
Predictive Modeling of Estradiol Effects and Sex Differences on Immunopathology during Influenza InfectionR01AI180382 · NIAID · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI Jason Edward Shoemaker · 2024 to 2026
$2.2M
Leveraging Pathogen-Host Networks to Identify Virus-specific and Estradiol-regulated Mechanisms during Respiratory InfectionR21AI174080 · NIAID · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI SHOEMAKER, JASON EDWARD · 2023 to 2024
$448k
Sex-specific Immune Responses to Severe Influenza Virus InfectionR21AI151418 · NIAID · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI SHOEMAKER, JASON EDWARD · 2021 to 2022
$427k
Mathematical Modeling of Influenza Severity in Outbred MiceR21AI153882 · NIAID · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI ALCORN, JOHN F, SHOEMAKER, JASON EDWARD · 2021 to 2022
$418k
NIAID NIH HHS R01 AI153209NIAID NIH HHS R01 AI160188NIAID NIH HHS R01 AI180382NIAID NIH HHS R21 AI151418NIAID NIH HHS R21 AI153882NIAID NIH HHS R21 AI174080NIAID NIH HHS UC7 AI180311NIGMS NIH HHS R01 GM115805
6 · The paper itself

Abstract

Eastern equine encephalitis virus (EEEV) is an arthropod-borne, positive-sense RNA alphavirus posing a substantial threat to public health. Unlike similar viruses such as SARS-CoV-2, EEEV replicates efficiently in neurons, producing progeny viral particles as soon as 3-4 hours post-infection. EEEV infection, which can cause severe encephalitis with a human mortality rate surpassing 30%, has no licensed, targeted therapies, leaving patients to rely on supportive care. Although the general characteristics of EEEV infection within the host cell are well-studied, it remains unclear how these interactions lead to rapid production of progeny viral particles, limiting development of antiviral therapies. Here, we present a novel rule-based model that describes attachment, entry, uncoating, replication, assembly, and export of both infectious virions and virus-like particles within mammalian cells. Additionally, it quantitatively characterizes host ribosome activity in EEEV replication via a model parameter defining ribosome density on viral RNA. To calibrate the model, we performed experiments to quantify viral RNA, protein, and infectious particle production during acute infection. We used Bayesian inference to calibrate the model, discovering in the process that an additional constraint was required to ensure consistency with previous experimental observations of a high ratio between the amounts of full-length positive-sense viral genome and negative-sense template strand. Overall, the model recapitulates the experimental data and predicts that EEEV rapidly concentrates host ribosomes densely on viral RNA. Dense packing of host ribosomes was determined to be critical to establishing the characteristic positive to negative RNA strand ratio because of its role in governing the kinetics of transcription. Sensitivity analysis identified viral transcription as the critical step for infectious particle production, making it a potential target for future therapeutic development.

Indexed as

Encephalitis Virus, Eastern EquineModels, BiologicalVirus ReplicationAnimalsBayes TheoremChlorocebus aethiopsComputational BiologyEncephalomyelitis, EquineHumansKineticsRibosomesRNA, ViralVirionRNA, Viral

Identifiers

PMID40465541
PMCPMC12136344

What OpenQuestion holds

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LicenceCC BY
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Registered trials

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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.