Antibodies against viral nucleo-, phospho-, and X protein contribute to serological diagnosis of fatal Borna disease virus 1 infections

Neumann, Bernhard; Angstwurm, Klemens; Linker, Ralf A.; Knoll, Gertrud; Eidenschink, Lisa; Rubbenstroth, Dennis; Schlottau, Kore; Beer, Martin; Schreiner, Patrick; Soutschek, Erwin; Böhmer, Merle M.; Lampl, Benedikt; Pregler, Matthias; Scheiter, Alexander; Evert, Katja; Zoubaa, Saida; Riemenschneider, Markus J.; Asbach, Benedikt; Gessner, André; Niller, Hans Helmut; Schmidt, Bárbara; Bauswein, Markus

doi:10.1016/j.xcrm.2021.100499

Cited by 23 publications

(42 citation statements)

References 14 publications

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“…The BoSOT study was conducted in an endemic region of southern Germany with recently confirmed BoDV-1 infections in humans and animals [ 18 , 21 ]. The study was approved by the Ethics Committee of the Faculty for Medicine, University of Regensburg, Regensburg, Germany (reference number: 21-2202-101) and registered in the DRKS trial register (DRKS00025180) on 4 May 2021.…”

Section: Methodsmentioning

confidence: 99%

“…As a control cohort for the serological epitope mapping, samples of patients with brain biopsies that tested negative for BoDV-1 by RT-qPCR and serum/plasma samples that tested negative for anti-BoDV-1-IgG by an indirect immunofluorescence assay (iIFA) and ELISA were used [ 18 , 21 ].…”

Section: Methodsmentioning

confidence: 99%

“…A BoDV-1 ELISA system using three different recombinant BoDV-1 proteins was performed as previously described [ 21 ]. Sequences for the BoDV-1 nucleoprotein (N), X protein, and phosphoprotein (P) were codon-optimized for expression in E. coli and cloned into the expression vectors pET30a, pGEX6P, and pET82, respectively.…”

Section: Methodsmentioning

confidence: 99%

“…Since the description of the first cases, more than 40 human infections associated with severe encephalitis have been reported to German health authorities. Most patients lived in the southern German state of Bavaria, but cases from the north and east of Germany have also been described [ 17 , 18 , 19 , 20 , 21 , 22 ]. As symptoms may resemble other severe neurological disorders such as Miller Fisher syndrome, Guillain-Barré syndrome, encephalopathy, or autoimmune encephalitis, diagnosis is not easy and the underreporting of cases is likely.…”

Section: Introductionmentioning

confidence: 99%

“…As symptoms may resemble other severe neurological disorders such as Miller Fisher syndrome, Guillain-Barré syndrome, encephalopathy, or autoimmune encephalitis, diagnosis is not easy and the underreporting of cases is likely. Especially in the initial stages or even during the whole disease period, cell counts in cerebrospinal fluid (CSF) can be normal or only slightly elevated [ 17 , 21 ], leading to difficulties with the timely initiation of diagnostic steps.…”

Section: Introductionmentioning

confidence: 99%

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Human Infections with Borna Disease Virus 1 (BoDV-1) Primarily Lead to Severe Encephalitis: Further Evidence from the Seroepidemiological BoSOT Study in an Endemic Region in Southern Germany

Bauswein

Eidenschink

Knoll

et al. 2023

Viruses

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More than 40 human cases of severe encephalitis caused by Borna disease virus 1 (BoDV-1) have been reported to German health authorities. In an endemic region in southern Germany, we conducted the seroepidemiological BoSOT study (“BoDV-1 after solid-organ transplantation”) to assess whether there are undetected oligo- or asymptomatic courses of infection. A total of 216 healthy blood donors and 280 outpatients after solid organ transplantation were screened by a recombinant BoDV-1 ELISA followed by an indirect immunofluorescence assay (iIFA) as confirmatory test. For comparison, 288 serum and 258 cerebrospinal fluid (CSF) samples with a request for tick-borne encephalitis (TBE) diagnostics were analyzed for BoDV-1 infections. ELISA screening reactivity rates ranged from 3.5% to 18.6% depending on the cohort and the used ELISA antigen, but only one sample of a patient from the cohort with requested TBE diagnostics was confirmed to be positive for anti-BoDV-1-IgG by iIFA. In addition, the corresponding CSF sample of this patient with a three-week history of severe neurological disease tested positive for BoDV-1 RNA. Due to the iIFA results, all other results were interpreted as false-reactive in the ELISA screening. By linear serological epitope mapping, cross-reactions with human and bacterial proteins were identified as possible underlying mechanism for the false-reactive ELISA screening results. In conclusion, no oligo- or asymptomatic infections were detected in the studied cohorts. Serological tests based on a single recombinant BoDV-1 antigen should be interpreted with caution, and an iIFA should always be performed in addition.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%