Tick-Borne Encephalitis Virus Adaptation in Different Host Environments and Existence of Quasispecies

Abstract

A highly virulent strain (Hypr) of tick-borne encephalitis virus (TBEV) was serially subcultured in the mammalian porcine kidney stable (PS) and Ixodes ricinus tick (IRE/CTVM19) cell lines, producing three viral variants. These variants exhibited distinct plaque sizes and virulence in a mouse model. Comparing the full-genome sequences of all variants, several nucleotide changes were identified in different genomic regions. Furthermore, different sequential variants were revealed to co-exist within one sample as quasispecies. Interestingly, the above-mentioned nucleotide changes found within the whole genome sequences of the new variants were present alongside the nucleotide sequence of the parental strain, which was represented as a minority quasispecies. These observations further imply that TBEV exists as a heterogeneous population that contains virus variants pre-adapted to reproduction in different environments, probably enabling virus survival in ticks and mammals.

How relevant are in vitro culture models for study of tick-pathogen interactions?

“…In contrast, in vitro TBEV infections maintained by serial passage in either tick or mammalian cells were reported to promote the selection of variants that exhibited distinct plaque sizes and virulence in a mouse model [78]. The selection of virus variants seems to be linked to the co-existence of several sequences in the parental strain, suggesting that viruses such as TBEV exist as a heterogeneous population (quasispecies) that contains virus variants pre-adapted to reproduction in different environments, probably enabling virus survival in ticks and mammals [79].…”

“…However, using in vitro models characterized by increasing complexity, from a cell line to an organ culture, it is possible to characterize many biological aspects of pathogen evolution, development, and interaction with the vector. This is most applicable to viruses, in which we can easily detect point mutations, recombination, or reassortment of genomes that give rise to new biological properties [78,79], while tick organ cultures offer as-yet unexplored possibilities to investigate tick-protozoan interactions at the cellular and molecular levels [56,58]. Of course, in vivo validation is required but in vitro models can speed up the progress of research and increase the number of laboratories working on tick-borne pathogens without the need for facilities and expertise to work with live infected ticks and host animals.…”

History of Arbovirus Research in the Czech Republic

“…They explained this as a process of selection of pre-existing virulent variants in the TBEV gene pool and not as the appearance of a new mutant [194]. The effect of passaging TBEV in different host cell systems was also observed by other investigators [195]. A highly virulent strain (Hypr) of TBEV was serially subcultured in the mammalian porcine kidney stable (PS) and I. ricinus tick (IRE/CTVM19) cell lines, producing three viral variants.…”

Heparan Sulfate Proteoglycans in Viral Infection and Treatment: A Special Focus on SARS-CoV-2

“…Thus, HS-positive cells merely adsorb the virus and do not contribute to replication or dissemination of the virus in vivo [ 92 ]. Attenuation of viral pathogenicity through the acquisition of HS-binding ability in cell cultures has also been reported for DENV [ 93 ], Sindbis virus [ 83 ], encephalitis viruses [ 94 ], foot and mouth disease virus [ 95 ], and others. On the other hand, in vivo HSPGs may not only facilitate the concentration of the virus at the cell surface, enhancing the probability of access to the related entry receptors, but they may also trap the viral particles at the surface of non-permissive cells and mediate in trans infection by allowing the virus to interact with entry receptors on permissive cells [ 96 , 97 ].…”

“…Of note, cell culture adaption mediated by HS may promote attenuation of viral virulence. Indeed, in some cases, HS attachment may inhibit rather than enhance the dissemination of HS-binding viruses [ 32 , 92 , 93 , 94 , 95 , 96 , 97 , 98 ]. A trapping effect of cell surface HSPGs has been demonstrated in vivo through the injection into mice of two enterovirus A71 mutants that resulted in a higher virulence of the HS-non-binding mutant with respect to that of the HS-binding one.…”