Wildebeest-derived malignant catarrhal fever: a peripheral T cell lymphoproliferative disease caused by gammaherpesvirus latency

Wildebeests carry asymptomatically alcelaphine herpesvirus 1 (AlHV-1), a gammaherpesvirus inducing malignant catarrhal fever (MCF) to several ruminant species (including cattle). This acute and lethal lymphoproliferative disease occurs after a prolonged asymptomatic incubation period following transmission. MCF has a significant socio-economical impact in regions where wildebeest inhabit and there is a strong need for affordable, safe and efficacious vaccine. Here, I will present the recent advances we have made on our understanding of the pathogenesis of this disease, from the generation of an AlHV-1 BAC clone to the demonstration that viral episomal maintenance by the latency-associated nuclear antigen-homolog (aLANA) is essential for inducing MCF. Based on these findings, a model can be proposed where latency-associated sudden and uncontrolled proliferation of activated cytotoxic CD8+ T cells in the periphery leads to MCF development. These findings will be presented in the light of recent unpublished findings and in the prospect of vaccine development.