Malignant catarrhal fever (MCF) is a lethal lymphoproliferative disorder of cattle and
deer caused by infection with either Alcelaphine herpesvirus - 1 (AHV-1) or Ovine
herpesvirus - 2 (OHV-2). The disease can be transmitted experimentally to rabbits.
Despite intensive studies, only very little viral expression can be detected in lesions.
It was therefore proposed that the viruses induce an interleukin-2 (IL-2)
hyperproduction which is responsible for the lymphoid cell hyperplasia observed.
In an initial comparative study, it was shown that all three viruses (AHV-1, OHV-2
and another bovid y-herpesvirus: Hippotragine herpesvirus- 1 (HipHV-1) induced
similar hyperplasia of lymphoid organs and accumulations of mononuclear cells in
non-lymphoid organs in rabbits. However, the different viruses affected preferentially
certain lymphoid organs. It was observed that the lymphoid cells in non lymphoid
tissues were CD43+ T-cells which showed evidence of in situ multiplication. A more
detailed phenotypic analysis of splenocytes and lymph node cells in AHV-1 infected
rabbits showed that the overall proportions of CD43, CD5, CD4, CDS and B-cells
were not altered, but that CD5+ and CD8+ cells were significantly enlarged.
The hyperplasia of lymph node cells was also investigated by examining the growth
characteristics of freshly explanted lymph node cells from AHV-1 infected rabbits.
The lymph node cells had a higher thymidine uptake respective to control cultures in
the first 24 hours. IL-2 increased viability and thymidine uptake and Con A did not
stimulate these cells as expected. Very little IL-2 activity could be detected in
supernatants from short term cultures using the CTLL-based bioassay. To establish a
RT-PCR/immunoblot for the detection of rabbit EL-2 mRNA, IL-2 cDNA from Con
A stimulated rabbit lymphocytes was cloned and partially sequenced. EL-2 transcripts
could be detected in lymphoid cells from pyrexic rabbits infected with AHV-1 and in
cells from control rabbits. Furthermore, it was shown that lymphoblastoid cell lines
(LCL) derived from MCF-affected cattle did not transcribe IL-2. These data lead to
the conclusion that DL-2 is involved in the acute state of MCF, but does not have a
central role in the pathogenesis.
Farther characterisation of IL-2 dependent LCL showed that they responded weakly
to Con A, were inhibited by Cyclosporin A and transcribed constitutively IL-4, IL-10,
INFy and TNFa, whereas no EL-1(3 mRNA could be detected. These data together
with the results derived from the short term cultures of lymph node cells from AHV1 infected rabbits clearly show that MCF inducing viruses alter the behaviour of
lymphoid cells. The possible interference of OHV-2 and AHV-1 with transductional
pathways, the expression of IL-2R and the activation of self-reacting lymphocytes is