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Dissecting Host-virus Interaction in Lytic Replication of a Model Herpesvirus

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Published on: October 7, 2011

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, Los Alamos, NM, United States.

Bioinformatics Advances

|July 13, 2026

Summary

This study enhances a virus evolution simulator to include human leukocyte antigen (HLA)-aware cytotoxic T-lymphocyte (CTL) responses, improving models of within-host virus sequence diversification and immune selection pressures.

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Area of Science:

Virology
Immunology
Computational Biology

Background:

Understanding virus sequence evolution under selection is crucial for vaccine design and transmission inference.
Modeling within-host virus evolution requires detailed frameworks capturing sequence diversification.
The CD8+ cytotoxic T-lymphocyte (CTL) response significantly impacts virus sequences but is often omitted in current models.

Purpose of the Study:

To extend the wavess within-host virus evolution simulator to incorporate an explicit HLA-aware CTL response.
To provide a method for identifying HLA-specific CTL epitopes from founder virus sequences.
To enable more accurate simulations of virus evolution, especially in immune-dominated regions.

Main Methods:

Extension of the existing wavess simulator to include an explicit CTL response.
Development of a method for HLA-specific CTL epitope identification.
Implementation of a variable recombination rate to model complex genomic structures.

Main Results:

The enhanced wavess simulator now explicitly models the HLA-aware CTL response.
The tool facilitates the identification of CTL epitopes relevant to immune selection.
The updated model allows for simulation of recombination across non-adjacent genes and segmented genomes.

Conclusions:

The extended wavess simulator provides a more accurate framework for modeling within-host virus evolution.
This advancement is particularly important for understanding viral evolution under CTL-mediated immune pressure.
The tool supports further research into how CTL responses and recombination influence viral sequence diversification.