Colocalization of hedgehog arterivirus 1 (HhAV-1) and histologic lesions in the European hedgehog (Erinaceus europaeus) with neurological disease

The European hedgehog (Erinaceus europaeus) is a protected species of conservation concern in the UK. In recent years, there have been multiple incidents of fatal encephalitis in captive hedgehogs in wildlife rescue centers associated with the molecular detection of a hedgehog arterivirus (HhAV-1). However, it remains unclear whether the virus is the causative agent of the central nervous system (CNS) lesions. In a retrospective investigation using postmortem material from 7 captive hedgehogs with neurological disease, and a single hedgehog with previously identified meningoencephalitis, histologic examination was conducted in tandem with viral RNA in situ hybridization (ISH) to appraise tissue distribution of HhAV-1 and the colocalization with histologic lesions. ISH revealed multicellular tropism of HhAV-1 involving monocyte-macrophage and vascular endothelial cells, with viral RNA detected in multiple organs, likely due to endotheliotropism and viremia. In the CNS, encephalomyelitis was mild whilst viral RNA was abundant and widely distributed, particularly in the microglial population and localized to areas with glial nodules. Splenic lymphoid depletion was generally mild but was moderate to severe in 2 septicemic animals. Brain samples from 13 control hedgehogs, found dead in the wild due to predation/trauma, were also screened for HhAV-1, of which 8 tested positive by real-time reverse transcription polymerase chain reaction (RT-PCR) with a low viral load. No CNS lesions or ISH labeling was observed in 2 of these control hedgehogs that could be examined histologically. Combined, these findings indicate that HhAV-1 infections in captive hedgehogs in English wildlife rescue centers may be associated with histopathologic alterations and clinical neurological disease.