In vivo models for rustrela virus (RusV) infection in potential reservoir and spill-over hosts

Rustrela virus (RusV; species Rubivirus strelense) is a recently discovered relative of the human rubella virus (Rubivirus rubellae) and causes fatal non-suppurative meningoencephalomyelitis in a broad range of mammalian domestic, wild and zoo animals, in Europe and the USA, including staggering disease in domestic cats. Based on its reportedly broad host range, a zoonotic potential of RusV cannot be excluded. Apparently healthy yellow-necked field mice (Apodemus flavicollis) and wood mice (Apodemus sylvaticus) were identified as potential reservoir hosts. In this study, we experimentally inoculated wood mice and Lewis rats with brain homogenates of RusV-infected animals. Intracranial as well as combined intranasal/peroral inoculation resulted in apparently persistent RusV infection in both rodent species, while combined intramuscular/subcutaneous injection failed to establish detectable infection. Viral loads were highest in the central nervous system, but viral RNA was prominently found also in mucosal organs of wood mice. Viral RNA was frequently detected in oral swabs from infected wood mice, but only sparsely from rats. Neither wood mice nor rats presented neurological signs during twelve weeks after infection. However, RusV-infected rats showed significantly reduced body weight. A lymphohistiocytic meningoencephalomyelitis was observed in infected rats, whereas infected wood mice infrequently developed minimal lesions in the brain. Our study provides the first infection model for RusV and indicates that natural infection may occur via mucosal routes. Shedding of viral RNA suggests wood mice to serve as natural reservoir hosts. In rats, we could reproduce a lymphohistiocytic meningoencephalomyelitis, as described for diseased cats and other tentative non-reservoir hosts.