Tick-borne encephalitis virus sequenced directly from questing and blood-feeding ticks reveals quasispecies variance

PLoS One. 2014 Jul 24;9(7):e103264. doi: 10.1371/journal.pone.0103264. eCollection 2014.

Abstract

The increased distribution of the tick-borne encephalitis virus (TBEV) in Scandinavia highlights the importance of characterizing novel sequences within the natural foci. In this study, two TBEV strains: the Norwegian Mandal 2009 (questing nymphs pool) and the Swedish Saringe 2009 (blood-fed nymph) were sequenced and phylogenetically characterized. Interestingly, the sequence of Mandal 2009 revealed the shorter form of the TBEV genome, similar to the highly virulent Hypr strain, within the 3' non-coding region (3'NCR). A different genomic structure was found in the 3'NCR of Saringe 2009, as in-depth analysis demonstrated TBEV variants with different lengths within the poly(A) tract. This shows that TBEV quasispecies exists in nature and indicates a putative shift in the quasispecies pool when the virus switches between invertebrate and vertebrate environments. This prompted us to further sequence and analyze the 3'NCRs of additional Scandinavian TBEV strains and control strains, Hypr and Neudoerfl. Toro 2003 and Habo 2011 contained mainly a short (A)3C(A)6 poly(A) tract. A similar pattern was observed for the human TBEV isolates 1993/783 and 1991/4944; however, one clone of 1991/4944 contained an (A)3C(A)11 poly(A) sequence, demonstrating that quasispecies with longer poly(A) could be present in human isolates. Neudoerfl has previously been reported to contain a poly(A) region, but to our surprise the re-sequenced genome contained two major quasispecies variants, both lacking the poly(A) tract. We speculate that the observed differences are important factors for the understanding of virulence, spread, and control of the TBEV.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Animals
  • Base Sequence
  • Child
  • Encephalitis Viruses, Tick-Borne / classification*
  • Encephalitis Viruses, Tick-Borne / genetics*
  • Encephalitis, Tick-Borne / blood
  • Encephalitis, Tick-Borne / virology*
  • Genetic Variation*
  • Humans
  • Male
  • Molecular Sequence Data
  • Nymph
  • Phylogeny
  • RNA, Viral / analysis
  • Sequence Analysis, RNA
  • Species Specificity
  • Ticks / virology*

Substances

  • RNA, Viral

Associated data

  • GENBANK/KF991106
  • GENBANK/KF991107
  • GENBANK/KF991108
  • GENBANK/KF991109
  • GENBANK/KF991110
  • GENBANK/KF991111
  • GENBANK/KF991114
  • GENBANK/KF991115
  • GENBANK/KF991116
  • GENBANK/KF991117
  • GENBANK/KF991118
  • GENBANK/KF991119
  • GENBANK/KF991120
  • GENBANK/KF991121
  • GENBANK/KF991122
  • GENBANK/KF991123
  • GENBANK/KF991124
  • GENBANK/KF991125
  • GENBANK/KF991126
  • GENBANK/KF991127
  • GENBANK/KF991128
  • GENBANK/KF991129
  • GENBANK/KJ960230
  • GENBANK/KJ960231

Grants and funding

This work was supported by grants to M. J. by The Foundation for Baltic and East European Studies and The Knowledge Foundation. Part of this study received financial support from EU through Interreg IV A to ScandTick (project ID 1672226) and Laboratory for Molecular Medicine Sweden (MIMS). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.