Alcelaphine herpesvirus 1 (AlHV-1), carried by wildebeest asymptomatically, causes malignant catarrhal fever
(WD-MCF) when cross-species transmitted to a variety of susceptible species of the Artiodactyla order.
Experimentally, WD-MCF can be reproduced in rabbits. WD-MCF is described as a combination of lymphoproliferation
and degenerative lesions in virtually all organs and is caused by unknown mechanisms.
Recently, we demonstrated that WD-MCF is associated with the proliferation of CD8+ cells supporting a latent
type of infection in lymphoid tissues. Here, we investigated the macroscopic distribution of AlHV-1 infection
using ex vivo bioluminescence imaging in rabbit to determine whether it correlates with the distribution of
lesions in lymphoid and nonlymphoid organs. To reach that goal, a recombinant AlHV-1 strain was produced
by insertion of a luciferase expression cassette (luc) in an intergenic region. In vitro, the reconstituted AlHV-1
luc+ strain replicated comparably to the parental strain, and luciferase activity was detected by bioluminescence
imaging. In vivo, rabbits infected with the AlHV-1 luc+ strain developed WD-MCF comparably to rabbits
infected with the parental wild-type strain, with hyperthermia and increases of both CD8+ T cell frequencies
and viral genomic charge over time in peripheral blood mononuclear cells and in lymph nodes at time of
euthanasia. Bioluminescent imaging revealed that AlHV-1 infection could be detected ex vivo in lymphoid
organs but also in lung, liver, and kidney during WD-MCF, demonstrating that AlHV-1 infection is prevalent
in tissue lesions. Finally, we show that the infiltrating mononuclear leukocytes in nonlymphoid organs are
mainly CD8+ T cells and that latency is predominant during WD-MCF.