Virology
Towards an understanding of Malignant Catarrhal fever at
the molecular level
Haig, D
SEERAD funded
Malignant Catarrhal Fever (MCF) is a fatal disease of cattle and other susceptible species such as deer and bison, caused by a family of gamma-herpesviruses including Alcelaphine herpsesvirus-1 (AlHV-1), which persistently infects wildebeest and causes MCF in cattle in East Africa, and Ovine herpesvirus-2 (OvHV-2), a widespread, persistent virus of sheep, which is the cause of sheep-associated MCF worldwide.
In the natural (reservoir) host, MCF virus infection is persistent and does not cause any overt disease. In contrast, infection of a susceptible host species causes MCF, with clinical signs similar to other important cattle diseases such as FMD, BVD and rinderpest. Early diagnosis is currently not possible as MCF is recognised only in the acute stages when the infected animal is near death. The route of infection is also not understood though the virus is assumed to be passed through close contact or via aerosol from the nasal/oral secretions of the reservoir host. The disease is sporadic but has serious consequences, since most animals showing clinical MCF either die or are culled. However, surveillance of this disease is difficult with traditional diagnostic tools due to the ability of the virus to persist for the lifetime of the reservoir host with little detectable virus or viral antigen.
MCF research at Moredun has three main goals:
• to improve the diagnostic tools available for MCF
• to understand how the virus causes disease in cattle
• to devise appropriate means for treatment and prevention
Little is known about how these viruses cause disease at this time. A central feature of MCF, however, is the emergence of promiscuously cytotoxic T cells that carry virus. In this project we studied AlHV-1 and OvHV-2 gene expression in infected T cells and analysed the function of expressed genes and their contribution to the cytotoxic phenotype and disease in model systems. We have developed methods to manipulate the viral life cycle in infected T cells; and we have shown that OvHV-2 encodes a functional version of the host interleukin-10 gene. This important regulator of immune responses is likely to be important in the development of MCF in cattle. These results will enhance our knowledge of the fundamental disease processes and may also have implications for the development of control and vaccination strategies for malignant catarrhal fever.
It is hoped that this research will also provide information that may be used to improve current viral surveillance and to advise end-users on best practise to reduce the occurrence of disease.