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Mystery of fatal 'staggering disease' unravelled: novel rustrela virus causes severe meningoencephalomyelitis in domestic cats.

ABSTRACT: '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.

SUBMITTER: Matiasek K

PROVIDER: S-EPMC9899117 | biostudies-literature | 2023 Feb

REPOSITORIES: biostudies-literature

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Mystery of fatal 'staggering disease' unravelled: novel rustrela virus causes severe meningoencephalomyelitis in domestic cats.

Matiasek Kaspar K Pfaff Florian F Weissenböck Herbert H Wylezich Claudia C Kolodziejek Jolanta J Tengstrand Sofia S Ecke Frauke F Nippert Sina S Starcky Philip P Litz Benedikt B Nessler Jasmin J Wohlsein Peter P Baumbach Christina C Mundhenk Lars L Aebischer Andrea A Reiche Sven S Weidinger Pia P Olofsson Karin M KM Rohdin Cecilia C Weissenbacher-Lang Christiane C Matt Julia J Rosati Marco M Flegel Thomas T Hörnfeldt Birger B Höper Dirk D Ulrich Rainer G RG Nowotny Norbert N Beer Martin M Ley Cecilia C Rubbenstroth Dennis D

Nature communications 20230204 1

'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 2 ...[more]

PMID: 36739288

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Project description:BackgroundStaggering disease (SD) is a severe neurological disease that has been regularly reported in Swedish cats since the beginning of the 1970s. The aetiology of SD has been debated, but novel rustrela virus (RusV) was recently suggested as the causative agent in Swedish cases dating from 2017 onwards. However, whether RusV was associated with earlier cases of feline SD in Sweden remained unknown. Further, presence of RusV in extraneural tissues of RusV-infected cats and viral transmission routes for RusV are still unknown. Therefore, we investigated the presence of RusV in nervous tissue of historical cases of plausible feline SD in Sweden, dating back to the 1970s, as well as the presence of RusV in selected extraneural tissues. Formalin-fixed, paraffin-embedded brain and spinal cord from 14 encephalitic cats matching the criteria for SD based on clinical and pathological records, and five non-encephalitic control cats were screened for the presence of RusV antigen and RNA using immunohistochemistry (IHC) and reverse transcription-quantitative polymerase chain reaction (RT-qPCR), respectively. Extraneural presence of RusV antigen was investigated by IHC in four known RusV-positive cats. Morphologic changes were evaluated using light microscopy. In addition, the 14 encephalitic cats were tested for Borna disease virus 1 (BoDV-1) RNA by RT-qPCR.ResultsMorphologic findings compatible with SD were confirmed in 13 of 14 encephalitic cats. All 13 cats were RusV-positive by IHC and 12 of them also by RT-qPCR. One encephalitic cat, morphologically and clinically untypical of SD, as well as all control cats tested negative for RusV RNA and showed either negative or uncertain RusV immunolabeling. There was no firm evidence of extraneural presence of RusV. All encephalitic cats were negative for BoDV-1.ConclusionsWe show that RusV has infected cats in Sweden as far back as the 1970s, whereas BoDV-1 was not detected in any of the investigated cats. This further strengthens RusV as the causative agent of feline SD. Our findings suggest that RusV is strongly neurotropic in cats and that the cat may represent a dead-end host. Further investigations into the pathogenesis of RusV-associated meningoencephalomyelitis in cats are warranted, including disease transmission, pathophysiologic responses and mechanisms of neuronal dysfunction.

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Mystery of fatal 'staggering disease' unravelled: novel rustrela virus causes severe meningoencephalomyelitis in domestic cats.

Publications

Mystery of fatal 'staggering disease' unravelled: novel rustrela virus causes severe meningoencephalomyelitis in domestic cats.

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