Are rabbits a suitable model to study sheep-associated malignant catarrhal fever in susceptible hosts?

Abstract

Sheep-associated malignant catarrhal fever (SA-MCF), caused by ovine herpesvirus 2 (OvHV-2), is an often fatal syndrome affecting mainly ruminants. SA-MCF pathogenesis and vaccine studies rely solely on live animals, since OvHV-2 has not been successfully propagated in vitro. Thus, the identification of a laboratory animal model is desirable and necessary to accelerate the identification of virus-host interactions that lead to disease. Rabbits are susceptible to infection with OvHV-2 and the disease can be reliably induced experimentally; however, the viral dynamics and host immune responses in the context of SA-MCF development in rabbits have not yet been evaluated. We addressed these knowledge gaps by experimentally infecting rabbits with OvHV-2 and monitoring viral and host infection parameters. Following intranasal nebulization of OvHV-2 in rabbits, the virus transiently replicates in the lungs inducing only subtle local inflammatory responses; the virus then disseminates systemically and increased levels of viral DNA and transcripts can be detected in multiple tissues as disease develops. The severity of lesions was shown to increase with both viral DNA copy number and expression levels of ORF25, ORF50 and ORF73. The events observed in rabbits following OvHV-2 infection occurred in the same fashion previously reported in bison, a natural clinically susceptible host. The results of this study in conjunction with previous reports demonstrate that rabbits are a valuable model for SA-MCF pathogenesis and vaccine studies.