Marek’s disease can be pervasive in chicken houses. Chickens infected by this highly contagious viral disease often develop tumors, become paralyzed and die. They can shed the virus through their skin, enabling it to linger in the environment for years, even decades. 

Vaccination controls the losses caused by Marek’s disease virus. In the United States, poultry producers have used a herpesvirus of turkeys (HVT) vaccine to combat Marek’s disease in chickens since the 1970s.

“It worked incredibly well, but the viruses that broke through replicated much faster and caused tumors more quickly,” said Mark Parcells, a University of Delaware professor of molecular virology.

By the mid-1980s, the U.S. implemented a combination of HVT with another vaccine. Then a different vaccine, commonly used in Europe, was licensed in the U.S. by the mid-1990s. 

Circumstances are different in Nigeria, where the virus has been circulating since the 1960s. It has cropped up frequently since the country’s poultry industry expanded in the 1980s. Rates continue to increase today, sending economic shockwaves through the country’s agricultural system.

Parcells along with several researchers, including Joseph Patria, a doctoral student in Parcells’ lab who graduated in August 2024, worry the virus will continue to get smarter and be able to mutate to resist vaccine efforts. 

“It’s important to continue vaccine research because you never know when you’re going to need a more effective vaccine,” Patria said.

In new research published in the journal Viruses, Parcells and colleagues at UD and in Nigeria and Germany suggest that outbreaks of Marek’s disease virus in Nigeria were caused by genetic variation in the viral oncogene, a gene called meq, that also apparently mediates resistance to vaccines. The findings give insight into how the virus could continue to evolve, not just in Nigeria, but along the Delmarva Peninsula, where the poultry industry is essential for the region’s economy.

Reading virus DNA

In 2012, Parcells attended an international Marek’s disease conference in France, where he met Luka Jwander, a state poultry veterinarian from Nigeria who told him the country was losing many laying hens to Marek’s disease. 

Parcells, who has been studying the disease and its virology since 1989, was instantly curious and interested in a partnership with Jwander.

UD researchers worked to get a special permit from the U.S. Department of Agriculture’s Animal and Plant Health Inspection Service (USDA APHIS) in order to import virus samples from Nigeria. Jwander sent UD’s Charles C. Allen Jr. Biotechnology Laboratory 40 samples from 12 farms in Nigeria’s Plateau State affected by increasing rates of Marek’s disease. 

The samples included tumor, blood and feather pulp spotted on special filter paper from chickens showing clinical signs of Marek’s disease virus (MDV). 

UD researchers extracted the DNA from the samples and worked to amplify the MDV meq oncogene, a gene essential for MDV’s ability to cause cancer, to look at its mutations. Parcells identified mutations in this gene that correlated with the virulence level of the virus encoding it in work published in 2004.

About the same time, it was discovered that the use of another vaccine (CVI988/Rispens), a Dutch vaccine widely used in Europe, apparently selected for higher virulence strains that also had mutations in meq, but in a different part of the meq gene than the part mutated in the high virulence strains of the U.S. 

By 2016 in Nigeria, the researchers noted some of the flocks were vaccinated against Marek’s disease virus at hatch with CVI988/Rispens (a strong vaccine) and then revaccinated with the U.S. herpesvirus of turkeys vaccine (a much weaker vaccine) at three weeks of age. This made it easier for the virus to break through if it overcame the strong vaccine.

The researchers ultimately found that the meq gene had mutations consistent with deadly European and deadly American field strains.

“So it was kind of the worst of both worlds,” Parcells said. 

Virus evolution

The research findings give scientists and the poultry industry insight into how Marek’s disease virus could evolve to be more severe. 

University of Delaware is a powerhouse research institution on poultry issues, touching every area of poultry from diseases to best management practices to litter quality. Parcells said the Nigeria-focused research gives the Delmarva poultry industry and researchers insight into the do’s and don'ts for protecting chickens against Marek’s disease virus. 

“At any given time, there can be mutations that can make vaccines ineffective,” Parcells said. “What happened in Nigeria tells us not to ever vaccinate with HVT, a somewhat weaker vaccine,  three weeks after chickens have already been vaccinated with the European vaccine CVI988/Rispens.” 

Parcells pointed out that as the poultry industry has evolved over the years, chickens are grown for less and less time before they’re ready to be processed into meat. On the Delmarva peninsula, broiler chickens tend to be alive for about seven weeks before they’re taken to a processing plant. That brings up concerns that the virus has a sort of pressure to infect its host faster.

“Control of Marek’s disease has been essential to poultry production worldwide,” Parcells said. "Current vaccination practices are working very well in the U.S., but these results suggest that re-vaccinating chickens with a weaker vaccine may provide pressure for field viruses to be able to overcome these practices and mutate.”

Patria said mutations of any virus can help scientists understand the virus’ severity. The method the researchers used to sequence the Marek’s disease virus gene could be used to monitor other viruses and outbreaks.

“It’s a feasible way to estimate the severity of a circulating virus or viral strain just by looking at the meq gene, the sequence variations within it, and how related it is to other strains,” Patria said. 

This information lets producers know if they have a higher virulence strain of virus affecting their flocks, or if chickens weren’t properly vaccinated at the hatchery. 

Parcells said researchers around the world have found that certain mutations in the meq gene always correlate with more severe viral strains.

“If these mutations are found, then more drastic changes have to be made in changing the vaccination strategy (using the CVI988 vaccine paired with another vaccine at hatch),” Parcells said. “If these are not found, then this suggests that there was a lapse in management practices at the hatchery (for example, they did not make the vaccine correctly, did not mix the vaccine well, or failed to vaccinate altogether).”

Patria is currently a postdoctoral research fellow at the University of Pennsylvania where he continues to pursue research in cancer virology. 

For one project, he is working to compare the sequence variation of high-risk Human Papillomavirus to investigate the nucleotide variations that are associated with head or neck cancer risks. The concept is similar to the approach he took to study Marek’s disease virus in chickens.

Continuing on the research, Parcells said he is working with research colleagues in Germany to dive more into what the mutations mean (how they affect the functions of meq). They hope to explore the ecology and evolution of the disease to understand how Marek’s disease virus changes as a result of vaccine use. The research could ultimately draw connections to some human diseases controlled by vaccines, for example, for Hepatitis B, Human Papillomavirus, and soon, Epstein-Barr Virus (which currently has vaccines in clinical trials). 

“We need to know how vaccine use may drive mutations of those viruses to maybe affect human cancers,” Parcells said.

About the research

The research paper, The Meq Genes of Nigerian Marek’s Disease Virus (MDV) Field Isolates Contain Mutations Common To Both European and US High Virulence Strains, is authored by Joe Patria, Mark Parcells, Brian Ladman, Levi Parcells, and Phaedra Tavlarides-Hontz of University of Delaware, Luka Jwander of the National Veterinary Research Institute in Nigeria, Ifeoma Mbachu of Lincoln University in Pennsylvania, and Jakob Trimpert and Benedikt Kaufer of Freie Universität Berlin. This work was supported by CANR seed grant funding to Mark Parcells. Students, Ifeoma Mbachu and Levi Parcells, were funded through USDA NIFA’s Envision program (NIFA REEU Award #2017-67032-26009 to Mark Parcells). 

This work is/was supported by the USDA National Institute of Food and Agriculture.

Any opinions, findings, conclusions or recommendations expressed in this publication are those of the author(s) and should not be construed to represent any official USDA or U.S. Government determination or policy.