Studies of the pathogenesis of Jembrana disease virus infection in Bos javanicus

Jembrana disease was reported initially in Bali cattle (Bos javanicus) on Bali island in 1964 and the causative agent was subsequently identified as a bovine lentivirus and designated Jembrana disease virus (JDV). This atypical lentivirus causes an acutely pathogenic disease that is associated with clinical signs and pathological lesions attributable to a disease primarily affecting the lymphoid system. Based on the intense proliferation of cells in the parafollicular (T-cell) areas of lymphoid tissue it has been assumed that the cellular tropism of the virus was for T-cells. An initial investigation of the pathological changes following JDV infection provided morphological evidence that JDV infection occurred not in T-cells but probably in centroblast-like cells containing IgG and presumably of B-cell lineage. The identity of the infected cells was confirmed by double immunofluorescence labelling techniques as being IgG-containing CD79α+ cells, indicating that the virus replicated in mature B-cells. Unlike other lentiviruses, no evidence of infection in T-cells or macrophages was obtained. These observations provide an explanation for suppression of the JDV-specific antibody response associated with JDV infection and the unique nature of the pathological response of Bali cattle to JDV infection. Flow cytometric analysis of peripheral blood leucocyte populations was used to further the understanding of the pathogenesis of JDV infection. Changes in lymphocyte subsets during the course of Jembrana disease were investigated and analysis of the results showed that lymphopenia, a characteristic of the acute febrile phase of Jembrana disease, was at least partly due to a significant decrease in CD4+ and CD8+ T-cells and CD21+ B-cells. In the immediate post-febrile recovery phase, virus-infected cells were not detected in lymphoid tissue but both CD8+ T-cells and CD21+ B-cells increased significantly and CD4+ T-cells remained below normal levels resulting in a significantly reduced CD4+:CD8+ ratio. Changes in expression of CD8+ T-cell regulated cytokine genes was examined during the course of the acute disease process by quantifying cytokine mRNA expression using real-time reverse-transcription polymerase chain reaction (RT-PCR). The results showed that both IL-2 and IFN-γ cytokine mRNA were strongly expressed during the febrile and early post-febrile recovery phases, which coincided with the significant increase of CD8+ T-cells and reduction of viraemia during this phase. The results suggested the CD8+ T-cell–associated cytokines IL-2 and IFN-γ probably play a significant role in the recovery process