‘Staggering disease’ is a neurological disease entity considered a threat to European domestic cats (*Felis catus*) for almost five decades. However, its aetiology has remained obscure. Rustrela virus (RusV), a relative of rubella virus, has recently been shown to be associated with encephalitis in a broad range of mammalian hosts. Here, we report the detection of RusV RNA and antigen by metagenomic sequencing, RT-qPCR, in-situ hybridization and immunohistochemistry in brain tissues of 27 out of 29 cats with non-suppurative meningoencephalomyelitis and clinical signs compatible with ‘staggering disease’ from Sweden, Austria, and Germany, but not in non-affected control cats. Screening of possible reservoir hosts in Sweden revealed RusV infection in wood mice (*Apodemus sylvaticus*). Our work indicates that RusV is the long-sought cause of feline ‘staggering disease’. Given its reported broad host spectrum and considerable geographic range, RusV may be the aetiological agent of neuropathologies in further mammals, possibly even including humans.

Kaspar Matiasek, Florian Pfaff, Herbert Weissenböck, Claudia Wylezich, Jolanta Kolodziejek, Sofia Tengstrand, Frauke Ecke, Sina Nippert, Philip Starcky, Benedikt Litz, Jasmin Nessler, Peter Wohlsein, Christina Baumbach, Lars Mundhenk, Andrea Aebischer, Sven Reiche, Pia Weidinger, Karin M. Olofsson, Cecilia Rohdin, Christiane Weissenbacher-Lang, Julia Matt, Marco Rosati, Thomas Flegel, Birger Hörnfeldt, Dirk Höper, Rainer G. Ulrich, Norbert Nowotny, Martin Beer, Cecilia Ley, Dennis Rubbenstroth