Marek Disease

An international team of scientists led by geneticists and disease biologists has used ancient DNA to trace the evolution of Marek's Disease Virus (MDV). This global pathogen causes fatal infections in unvaccinated chickens and costs the poultry industry over $1 billion per year. The findings show how viruses evolve to become more virulent and could lead to the development of better ways to treat viral infections. An international team of scientists led by geneticists and disease biologists from the University of Oxford and LMU Munich have used ancient DNA to trace the evolution of Marek's Disease Virus (MDV). This global pathogen causes fatal infections in unvaccinated chickens and costs the poultry industry over $1 billion per year. The findings, published today in the journal Science, show how viruses evolve to become more virulent and could lead to the development of better ways to treat viral infections. The team, which includes archaeologists and biologists, recovered and reconstructed ancient MDV sequences from archaeological chickens spanning the past 1,000 years. By comparing viral genomes derived from both modern and ancient birds, they were able to pinpoint the genetic alterations responsible for the increased virulence of the modern virus. Based on the ancient genetic sequences, they were also able to resurrect ancient biological processes using cellular assays, demonstrating that ancient strains were significantly milder than their modern counterparts. This breakthrough not only sheds light on the evolutionary history of MDV, but also holds promise for the development of more effective therapies against this devastating poultry disease. This new study is based on DNA isolated from chicken bones that were excavated from 140 archaeological sites in Europe and the Near East. These ancient genomes revealed that MDV was widespread in European chickens at least 1,000 years before the disease was first described in 1907. This highlights the importance of preserving archaeological remains, especially given their power to reveal valuable insights into the evolution of virulence. When first described, this disease only led to mild symptoms in older chickens. As chicken consumption dramatically increased in the 1950s and 1960s, MDV has continued to evolve and has become increasingly aggressive despite the development of several vaccines. First author Dr Steven Fiddaman (Department of Biology, University of Oxford) said: "Our findings not only unravel the evolutionary history of the Marek's Disease Virus but also provide a foundation for enhancing our current understanding of pathogen virulence. By combining ancient DNA techniques with modern genomics, we've opened a window into the past that can guide future strategies in managing viral diseases." Professor Naomi Sykes (University of Exeter), lead archaeologist on the study, stated: "This study underscores the profound significance of biological material preserved in archaeological and museum collections since we cannot foresee how their investigation might possess transformative applications in the future." Professor Laurent Frantz (LMU Munich), co-senior author of the study stated: "Our work highlights the power of interdisciplinary collaboration, bringing together paleogeneticists, virologists, archaeologists, and biologists to unravel the complex evolutionary history of a pathogen with significant economic and agricultural implications." Professor Greger Larson (University of Oxford), co-senior author commented: "We have seen how mitigating diseases often creates a selection pressure that increases the virulence of the virus. Being able to watch this process take place by sequencing ancient virus genomes shows just how dramatically the virulence of MDV has increased in the past century." Professor Adrian Smith (Department of Biology, University of Oxford), co-senior author said: "Ancient DNA has provided us with a unique perspective on the emergence of MDV as a deadly chicken virus and may teach us lessons that are applicable to the control of other viral infections of medical and veterinary importance." Professor Venugopal Nair, Scientist Emeritus at The Pirbright Institute, said: "Findings from this paper on the origins of virulence, particularly associated with the genetic sequences of the ancient Marek's disease viruses, will provide great scientific opportunities to explore the molecular mechanisms of increasing virulence of this virus that coincided with the intensification of poultry farming from the 1960s."

A study of a herpes virus that infects chickens offers new insights into potentially problematic interactions between vaccines made from live viruses and the viruses they are meant to thwart. A study of a herpes virus that infects chickens offers new insights into potentially problematic interactions between vaccines made from live viruses and the viruses they are meant to thwart. Reported in the journal Virulence, the study offers direct evidence that a vaccine and virus can infect the same cells in living animals and share molecular tools that allow the virus to infect other animals -- in this case, chickens. The study focused on Marek's disease, a viral infection that spreads when one chicken inhales fragments of dead skin or feather tissue from an infected chicken. "We've been trying to understand how the virus spreads from one host to another," said University of Illinois Urbana-Champaign pathobiology professor Keith Jarosinski, who led the research. "We're not only doing it for the benefit of the chickens in the poultry industry, but also because it's a very similar mechanism that the virus that causes chickenpox uses, where it enters through the respiratory route and infects the lymphocytes, and that gets it to the skin." The poultry industry has a practice of vaccinating newly hatched chickens against the Marek's disease virus, Gallid alphaherpesvirus 2. Some even vaccinate chicks in the egg, Jarosinski said. The use of live vaccines that have been modified so that they're not infectious is the most effective strategy for controlling symptoms of the disease, which include failure to thrive, tumors and death. Vaccines made from live viruses do a better job than other vaccines in training the immune system to recognize Marek's disease virus, but these vaccines do not lead to eradication of the virus, Jarosinski said. This leaves room for the natural virus and the modified viral vaccines to interact in ways that may promote viral evolution or infectiousness. Previous studies have shown that viruses can pick up genes from the vaccines designed to fight them, allowing the viruses to evolve in ways that sometimes boost virulence. But no studies have demonstrated that viruses and vaccines actually infect the same cells in live animals, Jarosinski said. Another potential interaction between viruses and vaccines involves a process known as "complementation," where vaccines, for example, produce a molecule that the virus can use to help it become infectious or more infectious, he said. The goals of the new study were to determine whether vaccines and natural viruses could infect the same cells in living chickens and to track whether a vaccine could supply a molecule that helps the virus spread to healthy chickens. To do this, researchers used a combination of viruses and vaccines, some of which contained all the genes for transmission and some that were modified in ways that rendered them unable to infect new hosts. This sometimes involved deleting the gene for a protein needed to enter cells and infect the new host. The researchers inoculated some chickens with both a virus and a vaccine and housed them with chickens that had not been exposed to either. Some of the inoculated birds were exposed to a nontransmissible form of the virus and a nontransmissible vaccine. Some were inoculated with a nontransmissible virus and a transmissible vaccine. The vaccines were tagged with a red fluorescent molecule and the nontransmissible virus was tagged with green, allowing the researchers to track the course of vaccine and viral infection in cells. A combination of red and green fluorescence yields yellow light, so only cells that glowed yellow were infected with both the virus and vaccine. The research revealed that some cells in inoculated birds contained both virus and vaccine -- the first demonstration of this phenomenon in live animals, Jarosinski said. The study also found that a Marek's disease virus that lacked a particular molecule needed for infection -- in this case a protein on the virus's outer envelope -- was able to pick up that molecule from a vaccine that had infected the same cell. This allowed the virus to infect new chickens. "Other studies haven't really shown that complementation between vaccines and viruses occurs except in artificial laboratory circumstances where they're using human-specific herpes viruses in mice or pigs, for example," Jarosinski said. "One of the unique things about this study is that we've looked at this process in a more natural model of infection, where we're using a virus that is specific to chickens in chickens." The study should not be used to spread alarm or panic, Jarosinski said, since complementation events are less worrisome than viruses swapping genes with vaccines. But the findings should inform the design of vaccines to eliminate potential attributes that might help viruses spread. The U.S. Department of Agriculture and the National Institutes of Health supported this research.