A NEW study from the University of California-Davis and the U.S. Department of Agriculture describes how vaccines work against a deadly virus in chickens and could offer a model for related human diseases such as chickenpox.

The study, published and highlighted in the November issue of the journal Vaccine, describes how three common vaccines for Marek's disease — a deadly herpesvirus disease in chickens — insert themselves into the chicken's chromosomes.

Herpesviruses in animals and humans have developed a number of strategies to evade the immune system and persist for later infection.

Mary Delany, animal science professor and poultry geneticist, said, "One of the key questions surrounding herpesviruses in animals and humans is: How do these viruses go latent, and where do they 'hide out' in cells of the body during a latent period, with the opportunity to re-emerge later?

"For example, the virus that causes chickenpox in children can seem to go away, only to reappear years later as a painful case of shingles in the adult," Delany said.

In earlier work, Delany and her colleagues showed that the Marek's disease herpesvirus integrates into the chicken's DNA, and the timing of that is associated with the timing of viral latency. This apparent strategy for evading the immune system allows the virus to persist in the cells of the host and potentially re-emerge later to cause infectious cycles.

Marek's disease is largely controlled by vaccination with related strains of the virus that prime the immune system to defend against the disease virus but do not cause disease themselves.

"In this recent study, we were quite surprised to find that Marek's vaccines also integrate into the host's chromosome, just as the disease-causing virus does," Delany said.

She noted that the chicken-based study has tremendous biomedical and economic implications, given that the chicken is one of the major sources of meat — as well as eggs — for much of the world.

Marek's disease, first described in 1907, is a highly contagious herpesvirus disease that, in chickens, causes recurrent infections and tumors within and among the organ systems.

Like other herpesviruses, the Marek's disease virus can transition from an active infection stage to a temporary latent stage. This enables the virus to evade the chicken's defensive immune system.

Marek's disease can be managed by selectively breeding for chickens with increased genetic resistance to the virus; however, vaccination is the predominant and most efficient method used to control — although not eradicate — the disease in commercial and even backyard chicken flocks.

The vaccines are prepared from related, weakened strains of the Marek's disease virus. Although they don't prevent infection, they do interfere with tumor formation and, therefore, prevent death in infected chickens.

However, even after 40 years of vaccinating chickens against Marek's disease, the exact mechanisms by which vaccines create immunity against the disease have not been clearly understood.

In response to vaccination, Marek's disease has evolved to ever more virulent forms. A better understanding of vaccine mechanisms should lead to the development of improved vaccines.

In this study, the researchers monitored chicks that had been vaccinated with one of three commonly used vaccines against Marek's, as well as a control group of chicks that had not been vaccinated.

They found that all three of the vaccine strains tested quickly integrated into the chicken genome, which is characteristic of virulent viruses. The chromosomal integration happened as early as one day after the chicks were vaccinated.

"It was completely unexpected that the vaccines would behave similarly to the disease-causing virus with regard to their interactions with the chicken genome," Delany said. "It was especially interesting that all three of these vaccines share the capacity to integrate into the genome, even though each shares different features with the Marek's disease virus."

She added that it is important to next determine whether the vaccines can re-emerge from their sites in the host genome to allow for long-lasting protection.

Her research group is now studying whether the vaccines may provide protection by out-competing the virus for a location in the host's genome, perhaps preventing latency and the creation of the specific cell population that can be transformed into deadly cancerous conditions.

"We need to find out whether genomic integration of the vaccine offers protection because it competes with integration of the disease-causing virus or if the vaccine's integration into the genome is simply an evolutionary relic that has no real function in protecting the bird," Delany said.

Swine virus

Researchers at Kansas State University have identified a new swine circovirus — porcine circovirus 3 — and its discovery is auspicious, because the related circovirus — porcine circovirus type 2 (PCV2) — has had a devastating history in swine production. Associated diseases caused millions of dollars in losses globally in the 1990s and early 2000s.

Porcine circovirus 3 — discovered by Benjamin Hause and Rachel Palinski with the Kansas State Veterinary Diagnostic Laboratory, along with collaborators at Kansas State University, Iowa State University and Smithfield Hog Production — is different from other known circoviruses, the university said.

"The Kansas State Veterinary Diagnostic Laboratory was sent samples from sows with signs of clinical disease typically caused by PCV2 infection; however, the samples were negative for PCV2," said Hause, an adjunct professor at Kansas State University's College of Veterinary Medicine. "Through further investigation, we identified an extremely novel, divergent new species of circovirus.

"We also performed polymerase chain reaction testing on random samples submitted to the lab to see how widespread this virus is in the U.S. swine herd. Twelve percent were positive for this new virus. We are hoping this is not the beginning of what could be a whole new epidemic of circovirus infections," he added.

The results of the discovery were published in the November issue of the Journal of Virology, which is produced by the American Society for Microbiology.

PCV2 was first identified in Canada in the mid-1990s during sporadic outbreaks of postweaning multisystemic wasting syndrome (PWMS), which causes young pigs to fail to thrive while they progressively lose body condition.

"PCV2 caused sporadic disease at first, but then there were massive epidemics of PMWS in Asia and Europe and in North America in the early 2000s," Hause said. "When I started working in the industry in 2005, this was about the height of this disease, and it literally killed millions and millions of pigs."

Hause said PCV2 vaccination has successfully controlled the disease, but it remains one of the most significant swine viruses.

"Now, we have a novel porcine circovirus that is distantly related to known circoviruses and that has been identified in sows with porcine dermatitis and nephropathy syndrome (PDNS) and reproductive failure," Hause said. "PCV2, which has previously been associated with these clinical presentations, was not identified here. This virus is clearly not a variant of PCV2 but a novel virus in its own right."

Hause said after the researchers discovered the new virus, they were able to check for its presence in archived samples.

"We detected porcine circovirus type 3 in aborted fetuses and in archival diagnostic cases of PDNS lesions that previously tested negative for PCV2," Hause explained. "Given the high economic impact of PCV2, this novel circovirus warrants further studies to elucidate its significance and role in porcine circovirus-associated disease."

Volume:88 Issue:12