Malignant catarrhal fever (MCF) is a fatal lymphoproliferative disease of Artiodactyla.
The disease is caused by infection of susceptible hosts with one of two
gammaherpesviruses, Alcelaphine herpesvirus-1 (AHV-1) or Ovine herpesvirus-2
On primary isolation, AHV-1 infectivity is cell-associated and the virus can induce
MCF following inoculation into susceptible hosts. Cell free virus which is pathogenic
for cattle is observed following low serial passage of the virus in cell cultures. After
further serial passage cell free virus is observed, but this virus cannot produce disease
experimentally. AHV-1 genomic rearrangements occur during the transition from
virulence to attenuation. Two genes, encoding putative protein 5 (P-5) and protein 1 (P1), are truncated during this rearrangement. The aim of this study was determine the
importance of these putative proteins in the pathogenesis of AHV-1.
Sequence encoding each of these proteins was cloned and the proteins expressed in
vitro. Rabbits, a laboratory model for AHV-1, were successfully immunised with these
proteins. Neither of these proteins however induced a protective immune response.
Although both proteins are expressed in vitro, transcripts for these proteins could not be
detected in vivo in animals reacting with MCF.
During the course of this study, the complete sequence of the AHV-1 genome was
published. P-l and P-5 were shown to form part of open reading frames (ORF) 50 and
A7 respectively. These ORFs were therefore re-assessed to determine their positions in
the attenuated and virulent virus. New isolates were obtained from cattle showing
clinical MCF and also from wildebeest. Analysis of viral DNA derived from the new
isolates has shown that ORF 50 and ORF A7 are conserved between isolates and the
virulent laboratory adapted isolate. The results presented here show that a block of
sequence in the attenuated virus, which includes sequence for ORF 50 and its promoter,
are translocated from a position in the middle of the unique DNA to a terminal position
where it is inverted with respect to its transcriptional orientation in the virulent virus.
The ORF is transcriptionally silent in the attenuated virus and the results presented here
show that this is due to the inactivity of the truncated ORF 50 promoter in the