The continuation of an apparent evolutionary trend of Marek's disease virus (MDV) towards greater virulence may explain recent increased losses from Marek's disease (MD) in vaccinated flocks. To address this question, the virulence of 31 isolates of serotype 1 MDV obtained from layer or broiler flocks between 1987 and 1995 were characterized. Each isolate was cultured in duck embryo fibroblasts for four to six passages, and ascertained to be free from contamination with avian retroviruses, chicken anemia virus, and MDVs of other serotypes. The viruses, along with prototype viruses JM/102W and Md5, were tested for virulence by inoculation at 6 days of age into laboratory strain 15I5 x 7(1) chickens of three types: nonvaccinated, vaccinated with turkey herpesvirus (HVT) and bivalent (HVT + SB-1)-vaccinated. The results showed that three isolates did not differ from JM/102W and were classified in the virulent (vMDV) pathotype. Twenty-one isolates produced significantly higher levels of MD in HVT-vaccinated chickens than did the JM/102W control and were classified in the very virulent (vvMDV) pathotype. Seven isolates, five of which were isolated in 1994 or 1995, produced significantly higher levels of MD in bivalent-vaccinated chickens than did the Md5 (vvMDV) control. These isolates, provisionally designated as the vv+MDV pathotype, appeared to be at the high end of a virulence continuum. Several MD response parameters, including lymphoma mortality, early mortality with bursal/thymic atrophy, and frequency of visceral lymphomas or ocular lesions in nonvaccinated chickens were positively correlated with virulence. These findings support the continued evolution of MDV towards greater virulence.

Increased Virulence of Marek's Disease Virus Field Isolates

SUMMARY Studies were conducted to determine whether a herpesvirus isolated from turkeys (HVT) would protect chickens against subsequent challenge with the virulent JM strain of Marek's disease herpesvirus (MDHV). HVT administered intra-abdominally at doses as low as 600 plaque-forming units per one-day-old chick gave protection against Marek's disease (MD). The virus would protect when birds were challenged with MDHV by intra-abdominal inoculation at 3 weeks or by contact exposure as early as 2 weeks postvaccination. Chickens inoculated with HVT and observed for 17 to 20 weeks did not develop lesions. Birds produced antibody and infection persisted throughout this period, however, as indicated by reisolation of the virus. Furthermore, HVT did not spread to chickens in direct contact with vaccinated birds. Thus HVT gives substantial protection against the development of MD yet is nonpathogenic and noncontagious, all of which are important characteristics of vaccine viruses.

Protection against Marek's disease by vaccination with a herpesvirus of turkeys.

Marek's disease virus (MDV) is an oncogenic herpesvirus that causes various clinical syndromes in its natural host, the chicken. MDV has long been of interest as a model organism, particularly with respect to the pathogenesis and immune control of virus-induced lymphoma in an easily accessible small-animal system. Recent advances in MDV genetics and the determination of the chicken genome sequence, aided by functional genomics, have begun to dramatically increase our understanding not only of lytic MDV replication, but also of the factors and mechanisms leading to latency and tumour formation. This new information is helping to elucidate cellular signalling pathways that have undergone convergent evolution and are perturbed by different viruses, and emphasizes the value of MDV as a comparative biomedical model. Furthermore, the door is now open for rational and efficient engineering of new vaccines against one of the most important and widespread infectious diseases in chickens.

Marek's disease virus: from miasma to model

A Marek's disease virus of low pathogenicity was isolated from a flock of chickens and was designated strain CVI 988. On primary isolation, this virus did not cause disease in susceptible chicks and gave excellent protection on subsequent challenge with a virulent virus, even if this challenge was performed shortly after vaccination. The virus occasionally caused minor microscopic lesions in antibody-free MD susceptible chicks but on further passage in DEF cultures the virus became completely avirulent while retaining its A antigen, spreading capacity and immunizing potentials. Chicks vaccinated by contact exposure developed a high degree of MD resistance after the 5th week but immunity was induced more rapidly when 3-week-old seeder chicks, which were actively shedding vaccine virus, were used as the source of exposure. However, by any procedure, contact-vaccinated chicks required several weeks for the development of solid immunity. High passage virus did not become virulent after 5 subsequent passages in antibody-free MD susceptible chicks. Vaccinated birds produced antibody which remained at a high level through observation periods of 2 years. Viremia and virus-shedding persisted throughout this period in a considerable number of birds. Rhesus monkeys inoculated with the virus did not develop any lesions during a one year observation period and no seroconversion could be detected.

Control of Marek's disease in the Netherlands. I. Isolation of an avirulent Marek's disease virus (strain CVI 988) and its use in laboratory vaccination trials.

The term pathogenesis is most simply defined as the development of disease. Many uncomplicated infectious diseases proceed in a direct fashion from infection to a specific pathologic expression. However, other diseases are relatively complex in terms of pathogenesis; Marek’s disease (MD) most certainly belongs in this category. This chapter will concern itself with the spectrum of sequential events triggered by infection with MD virus (MDV), and the consequences of those events at both the cellular and host level. It will also consider the many factors that affect the potential manifestations of MD. Attention will be given to mechanisms and interactions associated with those factors. Major emphasis will be placed on the lymphomagenic nature of the disease.

K Nazerian

Papers

Isolation from turkeys of a cell-associated herpesvirus antigenically related to Marek's disease virus.