The interferon system of non-mammalian vertebrates

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Abstract

Genetic analysis in mice and other mammals showed that the interferon (IFN) system is important for resistance to viral and bacterial infections. IFN is thought to play a similar role in non-mammalian species, although knowledge is lagging behind. Molecular cloning revealed low but significant conservation of IFN genes in birds and fish. Whereas chickens and other birds have multiple genes for IFN-α and single genes for IFN-β and IFN-γ like most mammals, fish appear to have fewer IFN genes. Nonetheless, regulation of IFN-α and IFN-β genes in response to viral and non-viral activators is well conserved in birds and fish, and similar sets of genes are induced in response to IFN in mammalian and non-mammalian vertebrates. IFN-like activities were also observed in reptiles and amphibians, but genes encoding these activities have not yet been cloned. Insights into the IFN system of non-mammalian species may lead to improved prophylactic and therapeutic approaches against virus infections in poultry and fish.

Introduction

Although interferon (IFN) was discovered in 1957 during experimental work with embryonated chicken eggs [1], the molecular analysis of IFNs from avian and other non-mammalian vertebrate species began only in 1994 [2] after most types of mammalian IFNs had already been characterized in great detail. Isolation of non-mammalian IFN genes proved very difficult mainly because the homology to their mammalian counterparts is low, thus severely aggravating the design of primer pairs suitable for RT-PCR. Interest in IFNs of birds and fish has recently sparked from increasing problems with viral diseases in the poultry industry and in aquaculture farming. In this review we will focus on recent progress towards a more detailed understanding of the biology of the avian and fish IFN systems.

Section snippets

IFNs of mammals: a brief overview

IFNs constitute a large group of cytokines that are best known for their ability to induce cellular resistance to viral pathogens [3], [4], [5]. They also play a critical role in the response to microbial infections by modulating the innate and adaptive immune system [6]. Furthermore, they are potent regulators of cell growth and can have inflammatory as well as anti-inflammatory effects [7], [8]. Two major types of IFN are known. IFN-γ, also called type II or immune IFN, is encoded by a single

IFNs of birds

Avian cytokine research started nearly half a century ago with the discovery of a virus-induced factor in embryonated eggs that interfered with influenza virus replication in chorioallantoic membranes of chicken embryos, hence the name IFN [1]. Early work in chickens focused on the purification of virus-induced IFN from embryonated eggs and chicken embryo cells [28], [29], [30]. It was described as a glycosylated polypeptide of 20–30 kDa with antiviral activity that was resistant to acid and

IFNs of fish

It has been known for many years that trout (Salmo gairdneri) can produce an IFN-like activity following virus challenge [56]. More recently, it has been demonstrated that leukocytes from the anterior kidney of trout are able to produce an antiviral response when stimulated with either poly I:C or infectious hematopoietic necrosis virus [57]. Leukocytes from rainbow trout stimulated with mitogen secreted a MAF activity into the supernatant that rendered a trout epithelial cell line resistant to

Interferon-like activities in reptiles and amphibians

An IFN-like activity in reptiles was demonstrated in primary turtle kidney cells (Testudo graeca). This factor, which was produced in response to virus infection, rendered normal turtle cells resistant to virus challenge [76]. It had a molecular weight of about 33 kDa, was acid-stable and heat-resistant. When peritoneal leukocytes from turtles were stimulated with Newcastle disease virus, poly I:C and endotoxin, antiviral mediators of higher molecular weight were secreted [76]. Antiviral

Conclusions and perspectives

From the available data summarized above, a picture emerges which shows that IFN is used by most, if not all, vertebrates. Over the last decade, IFN of birds was characterized at the molecular level and its biological activity was documented. At present, the potential beneficial effect of IFN is being evaluated in the poultry industry. Administration of IFN to birds might improve the efficacy of vaccines and enhance microbial resistance. Since a first gene for ZfIFN has recently been cloned,

Acknowledgements

This work was supported by a grant from the Deutsche Forschungsgemeinschaft (Schu1152/1-1).

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