Helmová et al.
Tick-borne encephalitis virus adaption in different host environments and existence of quasispecies
Viruses. 2020;12(8):E902. doi:10.3390/v12080902.
The TBE virus is carried by ticks and vertebrate hosts and must adapt to both systems to allow efficient replication. This may be done by a high adaptability (high error rate) of the RNA virus (RNA polymerase), yielding quasispecies which are closely related but not identical mutants. Such a genetically diverse virus populations would seem to have an adaptive advantage in a novel changing environment.
A Czech group has analyzed the development of quasispecies by serially subculturing of the TBE virus strain Hypr in the mammalian porcine kidney stable (PS) cell line and in parallel in the tick cell line IRE/CTVM19 – passaged 40 times producing the two new viral variants 40 PS and 40 IRE.
Between passages 20 and 30, virus replication rates in PS cells increased substantially. However, the plaque size (≥1.0 mm) did not change dramatically, while the virus selected in IRE/CTM19 cells changed considerably to 0.8 mm.
When the virulence was tested in a mouse model, a significant longer median survival time and lower mortality rate was observed in mice inoculated with 40 PS in comparison to the parental strain and the IRE-inoculated strain. Full-genome analyses of all variants showed that several nucleoside changes had occurred in different regions of the genome. The frequency of substitutions was higher in the mammalian cell-line passaged viruses in comparison to the tick-cell-derived variants. Amino acid exchanges were found in the gE, but also in prM and in non-structural proteins, e.g. NS2A. Mutations were also found in non-translated regions of the RNA. In summary, serial passaging and long-term persistent infection of tick cell lines do not result in attenuation of TBE virus in a vertebrate host. Plaque size in mammalian cells is not directly linked to the virulence of a TBE virus strain. There are certain mechanisms which allow rapid selection of adapted variants from pre-existing pool of viral variants (quasispecies).