Shuni virus (SHUV), an insect-transmitted orthobunyavirus of the Simbu serogroup within the family Peribunyaviridae, may induce severe congenital malformations when naïve ruminants are infected during gestation. Only recently, another clinical presentation in cattle, namely neurological disease after postnatal infection, was reported. To characterize the course of the disease under experimental conditions and to confirm a causal relationship between the virus and the neurological disorders observed in the field, six calves each were experimentally inoculated (subcutaneously) with two different SHUV strains from both clinical presentations, that is encephalitis and congenital malformation, respectively. Subsequently, the animals were monitored clinically, virologically and serologically for three weeks. All animals inoculated with the 'encephalitis strain' SHUV 2162/16 developed viremia for three to four consecutive days, seroconverted, and five out of six animals showed elevated body temperature for up to three days. No further clinical signs such as neurological symptoms were observed in any of these animals. However, four out of six animals developed a non-suppurative meningoencephalitis, characterized by perivascular cuffing and glial nodule formation. Moreover, SHUV genome could be visualized in brain tissues of the infected animals by in situ hybridization. In contrast to the 'encephalitis SHUV strain', in animals subcutaneously inoculated with the strain isolated from a malformed newborn (SHUV 2504/3/14), which expressed a truncated non-structural protein NSs, a major virulence factor, no viremia or seroconversion, was observed, demonstrating an expected severe replication defect of this strain in vivo. The lack of viremia further indicates that virus variants evolving in malformed foetuses may represent attenuated artefacts as has been described for closely related viruses. As the neuropathogenicity of SHUV could be demonstrated under experimental conditions, this virus should be included in differential diagnosis for encephalitis in ruminants, and cattle represent a suitable animal model to study the pathogenesis of SHUV.