A rabbit model for sheep-associated malignant catarrhal fever research: from virus infection to pathogenesis studies and vaccine development

Authors: Cunha, Cristina; O'TOOLE, DONAL - University Of Wyoming; Taus, Naomi; SHRINGI, SMRITI - Washington State University; KNOWLES, DONALD - Washington State University; Li, Hong

Submitted to: Current Clinical Microbiology Reports
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 7/3/2019
Publication Date: 7/17/2019
Citation: Cunha, C.W., O'Toole, D., Taus, N.S., Shringi, S., Knowles, D.P., Li, H. 2019. A rabbit model for sheep-associated malignant catarrhal fever research: from virus infection to pathogenesis studies and vaccine development. Current Clinical Microbiology Reports. 6:148-155. https://doi.org/10.1007/s40588-019-00126-3.
DOI: https://doi.org/10.1007/s40588-019-00126-3

Interpretive Summary: Sheep-associated malignant catarrhal fever (SA-MCF) is an often fatal disease that affects several animal species, including bison, cattle, deer and pigs. The disease is caused by a virus called ovine herpesvirus 2 (OvHV-2), which is carried asymptomatically by sheep. SA-MCF can have a significant economic impact on highly disease-susceptible hosts, such as American bison. The major goal in SA-MCF research is the development of a vaccine to protect animals from the disease. However, a drawback on achieving this goal is that OvHV-2 does not grow in cell culture and animal hosts have to be used for all experimental studies. In this scenario, having a laboratory animal model to use in experimental research is extremely valuable. In our previous studies, we demonstrated that SA-MCF can be reliably reproduced in rabbits and that infection parameters, such as dose- dependence, and clinical and pathological manifestations resemble those in natural hosts. The use of rabbits can significantly accelerate SA-MCF research; for instance, the model is critical to evaluate new vaccine candidates by allowing preliminary experiments to be performed in a laboratory animal prior to validation trials in large animals. In this review, key aspects of OvHV-2 infection and disease development in rabbits are presented and discussed in detail.

Technical Abstract: Purpose of review: Describe the implementation and use of rabbits as a laboratory model for sheep-associated malignant catarrhal fever (SA-MCF) research. Key considerations regarding the use of the model to generate consistent experimental data are presented and discussed in detail. Recent findings: A major drawback to SA-MCF research is that ovine herpesvirus 2 (OvHV-2), the etiological agent of SA-MCF, cannot be propagated in cell culture and experimental studies rely only on animals. An important research milestone was the finding that infectious cell-free OvHV-2 from nasal secretions of shedding sheep can be used to experimentally induce SA-MCF in various host species. Using this approach, we have demonstrated that rabbits can be infected with OvHV-2 and that infection parameters, such as dose-dependence, and clinical and pathological manifestations, resemble those in natural hosts. Summary: Rabbits are a reliable model for SA-MCF research and represent an important resource to the field. The model is especially useful to investigate virus-host interactions and evaluate MCF vaccine candidates.