In a study of the clinical response of cattle to infection with bovine ephemeral fever virus, thirty-nine cattle were experimentally infected and detailed clinical and haematological data were obtained from 10 of these animals. Inappetence was a major feature of the disease and occurred up to 24 hours before the onset of fever. The temperature response was characteristically biphasic with the second peak occurring 12 to 24 hours after the first. The only consistent haematological response was an increase in numbers of circulating neutrophils with a concurrent decline in numbers of mononuclear leucocytes. Changes in fibrinogen level s and in thrombocyte numbers were observed in only one animal. There were no changes in either plasma or blood volumes. Viraemia was demonstrated on either the first or second day of clinical disease and the longest detectable viraemia was 48 hours. Serum neutralising antibody could be detected 1 or 2 days after cessation of viraemia; addition of guinea pig complement to the test resulted in an apparent increase in antibody titres.
The major pathological lesion was a sero-fibrinous polyserositis involving the serosae of the synovial, pericardial and abdominal cavities. Experiments with the vascular permeability markers colloidal carbon and Evans blue demonstrated the presence of permeability changes in the endocardium and intima of large vessels as well as in vessels associated with serosal surfaces. Large numbers of neutrophils were present at sites of increased permeability and neutrophils were also present in large numbers in affected joint fluids and in fluids obtained from the pericardial, thoracic and abdominal cavities. Using a direct fluorescent anti body technique, viral antigen could be identified in many of these cells both in flu ids and in tissues. Viral antigen was also located within synoviocytes and epicardial serosal cells but it was not determined whether the antigen was present as a result of phagocytosis or replication.
In 3 cattle infected with virulent virus and depleted of neutrophils by daily injection of an equine anti-bovine neutrophil serum, no clinical signs developed nor could post-infection neutralising antibody be detected in spite of the presence of a detectable viraemia. Two of these animals developed clinical disease, viraemia and neutralising antibody when challenged 3 months later.
Peripheral blood neutrophils obtained before and during infection had equal phagocytic and killing abilities. Using anti- complementary and rosette- inhibit ion assays, evidence for the presence of antigen-antibody complexes in sera could be obtained from only one animal.
In a preliminary study of the cell mediated immune response to infect ion, no significant in vitro lymphocyte blastogenic response to antigen could be detected, probably due to incorrect antigen presentation. There was however a 200 fold increase in responsiveness to phytohaemagglutin in which may indicate an increase in the numbers of responsive circulating thymus derived lymphocytes, as a result of infection.
Relatively high levels of serum interferon could be detected at the time of viraemia and clinical disease in 6 infected cattle.
Inoculation of 3 water buffalo with virus of proven virulence for cattle resulted in viraemia without evidence of clinical disease in 2 animals and neither viraemia, clinical disease nor antibody in the other. In the 2 infected buffalo, titres of serum neutralising anti body persisted for less than 6 months.
Infection of adult mice with small doses of neurovirulent BEF virus resulted in a rapidly fatal encephalitis, the course of which was largely unaffected by treatment with cyclophosphamide, anti-thymocyte serum and immune cell transfer. Mice could be protected by treatment with defective virus, passive administration of antibody or by intra-dermal vaccination. Taken together these results emphasize the important protective role of antibody present at the time of infection. Viral isolation and immunofluorescent studies showed that the virus is confined to the central nervous system. Regular infection of suckling and adult mice by extra-cerebral routes was not possible. Adult mice were used to develop an intra-dermal vaccine which was used with partial success in cattle.