Submitted to: Avian Diseases
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 1/8/1997
Publication Date: N/A
Citation: N/A Interpretive Summary: Marek's disease virus is an important cause of economic loss in chickens. The virus has been gradually changing during the past 30 years so that current strains cause more disease than earlier ones. It is important to know the function of specific genes of the virus that determine different biological properties. Mutations caused by insertion of retroviral genes into Marek's disease virus are a tool to study these biological functions. We have studied one such mutant virus clone and found that the genes controlling virus growth and disease production are apparently different. Moreover, the data show that mutation of viral genes associated specifically with disease production resulted in a virus which provided very good protection against exposure to hot strains of Marek's disease virus. These findings contribute to our knowledge of gene function in Marek's disease and suggest ways to make better vaccines to control the disease.
Technical Abstract: Our earlier studies have shown that retrovirus insertion into herpesvirus is an efficient process which engenders recombinant herpesviruses with altered biological properties. The RM1 clone is derived from the JM strain of Marek's disease virus (MDV) through retrovirus insertional mutagenesis and contains sequences of reticuloendotheliosis virus (REV) inserted at the junction of the internal repeat and unique short regions of the genome. In previous studies, the RM1 clone appeared attenuated for oncogenicity but caused marked atrophy of the thymic lobes. The present studies represent a detailed analysis of the biological characteristics of the RM1 clone in order to better understand mechanisms of oncogenicity and gene function of MDV. RM1 was almost fully attenuated for oncogenicity but retained other in vivo properties of virulent viruses such as thymic and bursal atrophy, early immunosuppression, early cytolytic infection followed by efficient replication, and contact spread - all normally absent in attenuated strains. This suggests that oncogenicity of MDV is controlled by different viral genes or mechanisms than immunodepression and viral replication. The mutation was stable through serial passage of the virus in chickens as determined by molecular analysis. None of the mutant viruses demonstrated expansion of the 132 base pair repeat region of the genome, indicating that such expansion is not required for attenuation. Chickens vaccinated with RM1 clones were protected against challenge with virulent MDV and levels of protection exceeded those of other attenuated serotype 1 vaccine viruses. Thus attenuation by selective mutation may be an advantageous strategy for development of serotype 1 MD vaccines.