Treatment with anti-Pan T-cell antibody did not result in noticeable immune subset depletion. Detection of EBV DNA was higher in PBMCs in rabbits receiving

Epstein-Barr virus (EBV) is a gamma-herpesvirus that infects over 90% of the adult human population, causing most notably infectious mononucleosis, and is a known contributor to cancers such as Hodgkin and Burkitt lymphoma. While EBV is a species-specific virus, it has been studied in many animal models including non-human primates, guinea pigs, humanized mice, and tree shrews, but none are considered the gold standard for EBV research. Recently rabbits have emerged as a viable alternative model as they are susceptible to EBV infection, and the disease is able to progress after immune suppression with cyclosporine A (CsA), modeling the disease after proliferation of infected B-cells. We sought to refine this model to represent a primary EBV infection with concurrent immune suppression with either CsA or via antibodymediated depletion of immune subsets. Seven adult New Zealand White (NZW) rabbits were used to repeat the model of reactivation from latency, with treatment beginning 4 weeks postinoculation. Seven 3 month old to 1 year-old NZW rabbits were then used to model the primary form of the disease, receiving CsA concurrent to EBV inoculation. All rabbits receiving CsA followed a dosing schedule of 15 mg/kg SC at time 0, repeated for 4 days, then increased to 20 mg/kg SC twice weekly for two weeks. Finally, fourteen, 18 – 22 week old, NZW rabbits were inoculated with EBV intravenously and concurrently treated with either: anti-CD4 T-cell antibody, anti-Pan T-cell antibody, anti-HPV antibody (unrelated antibody control), or CsA. Rabbits receiving antibody were treated 3 times. Weights, temperatures, and clinical signs were monitored and rabbits were sedated once weekly for blood collection. Serial blood samples were analyzed by qPCR, flow cytometry, and ELISA. A novel imaging modality, the Toponome Imaging System (TIS), was utilized to obtain information on protein interactions in tissues from EBV infected rabbits. Samples of liver, spleen, and mesenteric lymph nodes were processed for histology. We found that treatment with anti-CD4 antibody resulted in fewer clinical signs compared to the CsA-treated rabbits, and higher levels of virus detection via qPCR in