The neuropathology of fatal encephalomyelitis in human Borna virus infection

Friederike Liesche,Gwendolyn Kaletka,Saida Zoubaa,Bruno Märkl,Jürgen Schlegel,Hans-Helmut Niller,Ines Lichtmannegger,Miguel Frederic Wachter,Bernhard Neumann,Kore Schlottau,Viktoria Ruf,Stefan Haschka,Christiane Herden,Georg Rieder,Markus J Riemenschneider,Kaspar Matiasek,Dennis Rubbenstroth,Lutz S Goehring ,Bárbara Schmidt ,W Permanetter ,Marco Rosati,Jonathan Jantsch,Christoph Brochhausen,Martin Beer,Bernhard Hemmer,Josef G Heckmann,Silke Wunderlich,Jochen Herms,Klemens Angstwurm,Arnt Ebinger

doi:10.1007/s00401-019-02047-3

Abstract

After many years of controversy, there is now recent and solid evidence that classical Borna disease virus 1 (BoDV-1) can infect humans. On the basis of six brain autopsies, we provide the first systematic overview on BoDV-1 tissue distribution and the lesion pattern in fatal BoDV-1-induced encephalitis. All brains revealed a non-purulent, lymphocytic sclerosing panencephalomyelitis with detection of BoDV-1-typical eosinophilic, spherical intranuclear Joest–Degen inclusion bodies. While the composition of histopathological changes was constant, the inflammatory distribution pattern varied interindividually, affecting predominantly the basal nuclei in two patients, hippocampus in one patient, whereas two patients showed a more diffuse distribution. By immunohistochemistry and RNA in situ hybridization, BoDV-1 was detected in all examined brain tissue samples. Furthermore, infection of the peripheral nervous system was observed. This study aims at raising awareness to human bornavirus encephalitis as differential diagnosis in lymphocytic sclerosing panencephalomyelitis. A higher attention to human BoDV-1 infection by health professionals may likely increase the detection of more cases and foster a clearer picture of the disease.

Highlights

The classical Borna disease virus 1 (BoDV-1; species Mammalian 1 orthobornavirus) can lead to lethal infections in a broad range of mammals
In 2015, the first human infections with another orthobornavirus were described, which resulted in lethal encephalitis of three breeders of variegated squirrels (Sciurus variegatoides)
Our study provides the first comprehensive description of the neuropathology of human BoDV-1 infection with focus on inflammatory lesions and virus distribution patterns at a systemic and cellular level

Summary

Introduction

The classical Borna disease virus 1 (BoDV-1; species Mammalian 1 orthobornavirus) can lead to lethal infections in a broad range of mammals. A severe neurological disorder (Borna disease) due to an encephalomyelitis lymphocytaria non-purulenta with loss of neurons had been described for accidental hosts [18]. Extended author information available on the last page of the article organism via the olfactory network and spreads through the limbic system to most cortical areas, brainstem, cerebellum, and spinal cord [9]. No report on confirmed human bornavirus infection existed. In 2015, the first human infections with another orthobornavirus (variegated squirrel 1 bornavirus [VSBV-1]; species Mammalian 2 orthobornavirus) were described, which resulted in lethal encephalitis of three breeders of variegated squirrels (Sciurus variegatoides).

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