Modeling the Epstein-Barr virus lifecycle in the rabbit

Epstein-Barr virus (EBV) is a human gammaherpesvirus that establishes a lifelong, persistent infection in greater than 90% of people worldwide. EBV has lacked an animal model that depicts the viral lifecycle in B cells and epithelial cells, allows for the investigation of immune responses, and models persistence in a host. EBV establishes a robust infection in immunosuppressed rabbits, resulting in widespread infection of the spleen and the development of splenomegaly. Within the spleen, follicle formation was altered as a result of EBV infection. Similar magnitudes of infection were observed in immunosuppressed rabbits infected with the B95-8 and Akata viral strains. In immunocompetent rabbits, spleen morphology appeared similar to that of mock-infected rabbits. Rabbits infected with B95-8 and Akata viruses developed antibody responses to the EBNA family of proteins in a comparable manner to human infection. Akata infections were more consistent in both the immunosuppressed and immunocompetent studies, whereas B95-8 infections resulted in variable magnitudes of infection and immune responses. The persistence of EBV in rabbits and whether the full lifecycle of EBV in lymphocytes can be replicated remain to be further examined.

The human gammaherpesvirus Epstein-Barr virus (EBV) infects more than 90% of the global population and is associated with lymphomas and carcinomas. EBV develops a lifelong, persistent infection in its host, avoiding immune detection by limiting the expression of its productive and latency genes. Currently, the EBV field lacks an animal model that can have persistent infection and immune responses to the virus during the course of infection. We demonstrated that rabbits mount an immune response to EBV infection over 6 months and may be a good model of persistent infection, although the viral genome remained below our limit of detection similar to humans.