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

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.