The Leeuwenhoek Lecture, 1997: Marek's disease herpesvirus: oncogenesis and prevention

Abstract

There are a number of neoplasias for which a herpesvirus is an essential part of the aetiology. Of these, Marek's disease is the most common and provides excellent opportunities for the study of a herpesvirus–induced tumour both experimentally and under natural conditions in the field. Marek's disease is caused by an alpha herpesvirus; it differs from the other oncogenic herpesviruses which are gamma herpesviruses. It is a ubiquitous virus in poultry populations of the world and is highly cell–associated and contagious, yet only a proportion of infected fowl develop tumours. Evidence is presented to suggest that at least one of the reasons for a wide variation in the incidence of the disease is a temporal interplay between virulent viruses and viruses of low or no virulence. The viral genes associated with the oncogenicity of Marek's disease virus (MDV) are discussed and it is concluded that it is likely that several genes are involved. Finally, a brief history of vaccination to control Marek's disease is given and mode of action discussed. It is concluded that the mechanism of protection is mainly through an antiviral cell mediated immune response, resulting in a lowered challenge virus burden. Marek's disease viruses over the past 40 years have been evolving greater oncogenicity, some of which are not adequately controlled by the vaccines that are currently available. It is suggested that for MDV to produce tumours, there is a need for the cytolytic infection phase and that infection must be with an MDV which possesses a functional gC , ICP4 for maintaining latency which allows the expression of at least the 1.8 kb family, pp38, meq , and possibly pp14 genes, for maintaining the tumour state and possibly initiating this state. Intervention in this process reduces the chance of tumour formation and incidence in a population which can occur through natural or man–mediated infection with non–pathogenic MDVs.