Die Bedeutung von Interferon alpha und Interferon gamma auf den Verlauf der Marekschen Krankheit beim Haushuhn

摘要

Marek´s disease virus (MDV) is a herpesvirus causing a lymphoproliferative disorder of domestic chickens worldwide. The early signs of disease like apathy, anorexy and the transient paralysis as well as the symptoms at the later stages (Neoplasia and death) causes large economical problems in the chicken industry. With the development of an effetive Vaccine, the first practical vaccine against an oncogenic disease of any type in any spieces, most of the serious problems were solved. However recent reports describing an increased virulence resulting in vaccine breaks, indicates a demand for better vaccines. To be able to enhance the prophylaxis against Marek´s disease virus, the understanding of the interaction between host and virus needs to be expanded.Interferons are cytokines with antiviral activity. On the basis of their structural and functional features they can be divided into type I (IFN-alpha and IFN-beta) and type II (IFN-gamma) interferons. Type I plays an important role during the early phase of viral infections, while IFN-gamma has a prominent role later during the infection through its immunmodulatory functions.In this study it was shown that chicken embryocellcultures responds to the infection with either an apathogenic strain of MDV (CVI 988) or a highly pathogenic strain (RB1B), with the secretion of an antiviral factor. Neutralisation with cytokine specific antibodies revealed that this activity could only be attributed to IFN-alpha but not IFN-beta. In addition, synthesis of IFN-gamma was not observed in any of the experiments.Treatment of MDV infected embryocellcultures with either recombinant chicken IFN-alpha (rChIFN-alpha) or recombinant chicken IFN-gamma (rChIFN-gamma) led to a significant reduction in plaque numbers. This antiviral effect was still observed when cultures were treated 48 hours after infection.In order to understand the functional role of the IFNs in vivo, leghorn birds were repeatedly treated with rChIFN-alpha or rChIFN-gamma for ten weeks starting on the day of hatch. The birds were then challanged on the second day of life with a highly virulent MDV-strain (vv+, EU-1).Treatment with IFN-gamma delayed the mortality to a very small degree. In contrast, IFN-alpha treatment delayed the mortality for 3 weeks. However, prevention of the disease was not achieved regardless of the used IFN-alpha dose. The functional relevance of IFN-alpha was further underscored by experiments where birds were treated with a neutralizing monoclonal antibody to ChIFN-alpha and thereafter infected with the EU-1 strain at the second day of life. Birds in this group died 3 weeks earlier than those in the untreated control group.These data shows that Interferons play a role in the progression of Mareks disease, however, regardless the IFN-dose applicated, the disease could not be prevented by the cytokines on their own.