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

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.