Tracking the evolution of Marek’s disease virus using ancient DNA

• Applicant: Professor Dr. Laurent Frantz, Ph.D.
• Subject Area: Veterinary Medical Science ; Evolution, Anthropology ; Virology
• Term: since 2022
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 497793864

Marek’s disease (MD), caused by a highly contagious oncogenic alphaherpesvirus known as Marek’s virus (MDV) is one of the most ubiquitous diseases in the poultry industry costing >1 billion USD every year. Over the second half of the 20th century MDV has evolved into a highly virulent virus, and the strains that are now circulating can kill 100% of unvaccinated chickens in less than 10 days, requiring nearly every chicken hatched by the global poultry industry to be vaccinated. The reasons for this increased virulence is likely the result of imperfect vaccination against MDV which allows the virus to circulate in a large fraction of the 25 billions chickens raised across the globe. This increased rate of transmission is expected to have dramatically elevated MDV’s rate of molecular evolution, resulting in both multiple episodes of vaccine evasion and the apparition of increasingly more severe symptoms in infected chickens. In fact, the evolution of MDV is such that all naturally occurring strains known today are all disease causing, and as a result little is known about the genetic variability associated with naturally occurring non-virulent strains. Knowledge of genetic variability in non-virulent strains, however, could be highly valuable for the development of more efficient vaccines.Our preliminary results demonstrate that MDV genomes can be recovered from ancient chicken bones that were excavated at archeological sites across Europe using state-of-the-art ancient DNA techniques. In fact, we show that MDV was likely circulating perhaps as early as 800 years before the first report of MD. Here we aim to use state-of-the-art ancient DNA techniques to sequence and analyse ancient MDV genomes to 1) identify genetic variability that differentiate strains prior to, and after, the episode of increasing virulence of the 20th century, and 2) to assess whether this virus did evolve faster during this period. Altogether, the result of this study will shed light on the evolutionary history of one of perhaps the most ubiquitous pathogens in the livestock industry and will potentially provide key candidate mutations for rational attenuation of MDV strains to improve vaccination.

• DFG Programme: Research Grants