Novel variants of tick-borne encephalitis virus from patient and tick samples in Norway

The annual number of tick-borne encephalitis (TBE) cases in Norway has increased dramatically from 1 case in 1998 to 113 in 2023. Characterization of TBE virus (TBEV) genomes from both clinical samples and tick vectors is necessary to understand disease severity and transmission dynamics. However, clinical samples with intact virus are rare because TBE is usually diagnosed by serology in the post-viremic phase, when the viral load is low and undetectable by molecular methods such as polymerase chain reaction (PCR). To date, Mandal-2009 is the only TBEV sequence from Norway with complete virus genome, sequenced directly from the tick vector. We used a combined approach with newly designed overlapping primer pairs and nanopore sequencing together with Sanger sequencing to obtain nearly complete TBEV genomes from both patient and tick samples from Norway. The patient had severe TBE complicated with hemophagocytic lymphohistiocytosis (HLH). The patient and tick samples were collected 16 km apart, from Telemark and Vestfold Counties, respectively. Pairwise genomic comparison showed 99.7 % identity, and phylogenetic analysis revealed that these sequences were closely related to the TBEV strain from Kumlinge in Åland, Finland, rather than to the previously published Norwegian variant Mandal-2009. These findings confirm the existence of novel TBEV variants in the endemic areas of Telemark and Vestfold Counties of Norway. Our findings highlight the need for continuous monitoring and characterization of novel TBEV genomes in Norway and Europe.