Transcriptional and translation shut-off in TBEV infected neural cells and involvement of viral C protein

Tick-borne encephalitis virus (TBEV, Flaviviridae) infection causes severe neurological disease and incapacitates more than 10 000 patients annually in the Eurasian region. Despite extensive studies, some areas of interaction of TBEV with the host cells remain undescribed. Here we investigated the interaction of TBEV and human neural DAOY HTB-186 cells on the transcriptional and translational level.

By labelling of nascent RNA and protein molecules in TBEV-infected DAOY cells, we showed that the virus-induced host translational shut-off. Moreover, TBEV interfered also with the expression of host ribosomal RNAs, in particular with the rRNA species transcribed by RNA polymerase I (18S rRNA, 28S rRNA, and their precursor 45-47S pre-rRNA). Synthesis of host rRNAs is an essential host cell process that is localized in the nucleus, namely nucleoli. By searching for virus factor that could be linked with these effects, we described so far unknown nucleolar localization of TBEV capsid protein C. More importantly, preliminary data from transfection of recombinant C protein led to the reduction in nascent protein synthesis indicating the link between TBEV capsid protein and shut-off phenomena which were described. Furthermore, we identified a potential nuclear localization signal, which seems not to be essential for the shut-down effect.

Taken together we described a brand new type of interaction between TBEV and host neural cells on the transcriptional and translational level and identified viral factor potentially responsible for the observed phenomena. However, further analyses are needed, and the particular mechanism of action remains still elusive.