Speaker
Description
Marek’s disease (MD) provides a well-documented model for researching imperfect vaccines and viral vaccine escape dynamics. Despite more than 50 years of vaccination programmes, MD remains prevalent worldwide in the chicken industry. The vaccines are “leaky”, allowing low level persistence and transmission of Marek’s disease virus (MDV), the causative oncogenic herpesvirus. Resistance has developed to each in a series of vaccines concomitant with increasing disease severity, likely caused by the evolution of vaccine-escape strains towards greater virulence.
We sought to examine the phylodynamics of 60 MDV strains isolated in the USA from 1965 to 2014. Illumina reads were subjected to reference-based assembly, giving an average coverage depth of 830. Using Bayesian MCMC analysis in BEAST, substitution rates were inferred for the full genome (1.46 x 10-5 s/s/y) and individual genes (6.07 x 10-6 to 8.25 x 10-4 s/s/y). Further, we implemented a skygrid model to infer effective population dynamics at gene level with respect to the serial implementation of the 3 prevailing vaccines, and identified individual gene responses in these eras. Diversity expansion following bottleneck events was measured and compared in instances of diversity rebound, and 9 genes exhibited a greater than 3-fold increase in diversity expansion rate.
Using MD as a model to study vaccine-induced virus evolution, we investigated phylodynamics in a collection of MDV field strains isolated over a 50-year period. Rapidly evolving genes were identified through substitution rates. Combining effective population curves with known dates of vaccine usage, we were able to infer vaccine effects on gene diversity dynamics. Whilst some genes appeared unaffected by vaccine usage, others underwent bottleneck events in response to 1 or more vaccines. A subsequent rebound in diversity occurred for some of these genes suggestive of a role in vaccine escape and increasing virus virulence.
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