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Updated: May 27, 2026

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wavess 1.2: Presenting an HLA-aware within-host virus sequence simulation framework.

Zena Lapp1, Thomas Leitner1

  • 1Theoretical Biology and Biophysics, Los Alamos National Laboratory, New Mexico, United States of America.

Biorxiv : the Preprint Server for Biology
|February 27, 2026
PubMed
Summary

This study enhances a virus evolution simulator to include the CD8+ cytotoxic T-lymphocyte (CTL) response and variable recombination rates. This improves modeling of within-host virus sequence diversification, crucial for vaccine design and transmission inference.

Keywords:
immunologymolecular evolutionrecombinationsimulationvirology

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Area of Science:

  • Virology
  • Immunology
  • Computational Biology

Background:

  • Understanding virus sequence evolution under selection is vital for vaccine development and inferring transmission.
  • Within-host virus evolution modeling requires detailed mechanistic frameworks to capture sequence diversification accurately.
  • The CD8+ cytotoxic T-lymphocyte (CTL) response significantly influences immune-mediated selection on virus sequences, but is often omitted in current models.

Purpose of the Study:

  • To extend an existing within-host virus sequence evolution simulator (wavess) to incorporate an explicit HLA-aware CTL response.
  • To develop a method for identifying HLA-specific CTL epitopes from founder virus sequences.
  • To enable more accurate simulation of virus evolution, particularly in immune-selected regions, and investigate the impact of recombination.

Main Methods:

  • Extended the wavess simulator with an explicit CTL response module.
  • Implemented a method for identifying HLA-specific CTL epitopes.
  • Updated the model to allow for variable recombination rates, accommodating hotspots and segmented genomes.

Main Results:

  • The enhanced wavess simulator provides more accurate simulations of virus evolution, especially in CTL-dominated immune response regions.
  • The inclusion of HLA-specific CTL epitopes and variable recombination rates allows for detailed investigation of within-host evolutionary dynamics.
  • The updated model serves as a foundation for studying how these biological mechanisms impact virus sequence diversification.

Conclusions:

  • The enhanced wavess simulator offers a more comprehensive tool for studying within-host virus evolution.
  • Accurate modeling of CTL responses and recombination is essential for understanding virus adaptation and informing public health strategies.
  • This work facilitates deeper insights into virus-host interactions and evolutionary trajectories.