Abstract

Next-generation sequencing (NGS) has opened up the possibility of detecting new viruses in unresolved diseases. Recently, astrovirus brain infections have been identified in neurologically diseased humans and animals by NGS, among them bovine astrovirus (BoAstV) CH13/NeuroS1, which has been found in brain tissues of cattle with non-suppurative encephalitis. Only a few studies are available on neurotropic astroviruses and a causal relationship between BoAstV CH13/NeuroS1 infections and neurological disease has been postulated, but remains unproven. Aiming at making a step forward towards assessing the causality, we collected brain samples of 97 cases of cattle diagnosed with unresolved non-suppurative encephalitis, and analyzed them by in situ hybridization and immunohistochemistry, to determine the frequency and neuropathological distribution of the BoAstV CH13/NeuroS1 and its topographical correlation to the pathology. We detected BoAstV CH13/NeuroS1 RNA or proteins in neurons throughout all parts of the central nervous system (CNS) in 34% of all cases, but none were detected in cattle of the control group. In general, brain lesions had a high correlation with the presence of the virus. These findings show that a substantial proportion of cattle with non-suppurative encephalitis are infected with BoAstV CH13/NeuroS1 and further substantiate the causal relationship between neurological disease and astrovirus infections.

Highlights

  • The first interest in viral infections of the central nervous system (CNS) dates back to antiquity [1], but neurovirology has only recently become a growing field with the discovery of less invasive techniques of surgery and diagnostic sampling in the late 20th century

  • In 27 bovine astrovirus (BoAstV) CH13/NeuroS1 positive cases the staining in the IHC was comparable to the one in the in situ hybridization (ISH), in the region and in the number of cells affected by the virus

  • Since animals under investigation were at different stages of the disease and the intensity of lesions was variable between individuals, we propose that different CNS infection stages may be accountable for these results

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Summary

Introduction

The first interest in viral infections of the central nervous system (CNS) dates back to antiquity [1], but neurovirology has only recently become a growing field with the discovery of less invasive techniques of surgery and diagnostic sampling in the late 20th century. Non-suppurative encephalitis is an inflammatory pattern observed in the context of post-mortem histopathological brain examinations and is indicative of viral infections. In Switzerland, non-suppurative encephalitis has been diagnosed in approximately 15% of neurologically-diseased cattle, but in many cases the etiology could not be determined and remained unknown [12,13,14,15]. These cases occurred sporadically and in single animals and were designated as “European sporadic bovine encephalitis” (ESBE). It has yet to be determined whether these cases of non-suppurative encephalitis were caused by a single virus, or instead by several different viruses

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