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

Borna disease virus 1 (BoDV-1) can cause rare but fatal encephalitis in humans, often diagnosed too late for an experimental therapeutic approach. In a recent case of fatal BoDV-1 infection, BoDV-1 RNA was detected in cerebrospinal fluid (CSF) on day 12 after hospital admission. Seroconversion in this and seven previous cases was confirmed using a newly developed ELISA with recombinant BoDV-1 nucleoprotein, phosphoprotein and accessory protein X. For each recombinant BoDV-1 protein, an individual cut-off was determined by 24 negative sera. To assess the specificity of the ELISA, we took advantage of an independent cohort of 56 patients with suspected tick-borne encephalitis, whose serum/plasma samples were screened for BoDV-1 IgG antibodies for diagnostic purposes. Corresponding CSF samples of all patients were tested negative for BoDV-1 by RT-qPCR. Our findings demonstrate that early detection of BoDV-1 RNA in CSF and the presence of antibodies against at least two different viral antigens contribute to BoDV-1 diagnosis. Physicians in endemic regions should consider BoDV-1 infection in unclear encephalopathy, even with normal CSF leucocyte counts, and initiate appropriate diagnostics at an early stage.