Kravchuk et al.
Cross-reactive antibodies to the NS1 protein of Omsk hemorrhagic fever virus are absent in the sera of patients with tick-borne encephalitis. Viruses. 2024;16(7):1032. doi:10.3390/v16071032

Omsk hemorrhagic fever virus (OHFV) belongs to the tick-borne encephalitis virus complex of the Flaviviridae family. Clinical symptoms following an OHFV infection resemble those caused by the tick-borne encephalitis (TBE) virus, but in addition, hemorrhagic manifestations can occur. OHF has been reported from several regions of Russian Siberia (see e.g. Snapshot week 38/2022), and recently also from Kazakhstan (see Snapshot week 26/2022).

Due to cross-reactivity of antibodies directed to the glycoprotein E, commercial ELISA kits and neutralization assays cannot be used to differentiate between an OHFV and TBE virus infections. An alternative suitable target for the different serological diagnosis of flavivirus infections is the non-structural protein 1 (NS1). Various diagnostic tests based on NS1 have been developed to differentiate between flavivirus infections (e.g. Saint Louis encephalitis and West Nile virus infections), and to discriminate between antibodies produced after an infection by TBE virus from antibodies induced after vaccination (see e.g. Snapshot week 26/2021, Newsletter April 2020).

NS1 of OHFV (strain 186-1964) was recombinantly expressed in E. coli. The nucleotide identity to NS1 of TBE virus was 80.1%. Immune ascites fluids from mice independently infected with two different strains of OHFV reacted in an ELISA based on this recombinant NS1 antigen, but not when NS1 of TBE virus strain Sofjin was used as antigen. In Western blot analyses, various monoclonal antibodies to NS1 of OHFV detected recombinant OHFV-NS1, while mabs to TBE virus NS1 did not. In an ELSA based on OHFV-NS1, 95% of TBE patient sera containing antibodies to NS1 were not recognized in this test system.

These results indicate that OHFV-NS1 has an antigenic structure different from TBE virus NS1 and could potentially been used as an antigen for differential diagnosis of TBE and OHF.

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