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Replication enhancer elements within the open reading frame of tick-borne encephalitis virus and their evolution within the Flavivirus genus
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Tuplin, Andrew, Evans, David J., Buckley, A., Jones, I. M. (Ian M.), Gould, E. and Gritsun, T. S. (2011) Replication enhancer elements within the open reading frame of tick-borne encephalitis virus and their evolution within the Flavivirus genus. Nucleic Acids Research, Vol.39 (No.16). pp. 7034-7048. doi:10.1093/nar/gkr237 ISSN 0305-1048.
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Official URL: http://dx.doi.org/10.1093/nar/gkr237
Abstract
We provide experimental evidence of a replication enhancer element (REE) within the capsid gene of tick-borne encephalitis virus (TBEV, genus Flavivirus). Thermodynamic and phylogenetic analyses predicted that the REE folds as a long stable stem-loop (designated SL6), conserved among all tick-borne flaviviruses (TBFV). Homologous sequences and potential base pairing were found in the corresponding regions of mosquito-borne flaviviruses, but not in more genetically distant flaviviruses. To investigate the role of SL6, nucleotide substitutions were introduced which changed a conserved hexanucleotide motif, the conformation of the terminal loop and the base-paired dsRNA stacking. Substitutions were made within a TBEV reverse genetic system and recovered mutants were compared for plaque morphology, single-step replication kinetics and cytopathic effect. The greatest phenotypic changes were observed in mutants with a destabilized stem. Point mutations in the conserved hexanucleotide motif of the terminal loop caused moderate virus attenuation. However, all mutants eventually reached the titre of wild-type virus late post-infection. Thus, although not essential for growth in tissue culture, the SL6 REE acts to up-regulate virus replication. We hypothesize that this modulatory role may be important for TBEV survival in nature, where the virus circulates by non-viraemic transmission between infected and non-infected ticks, during co-feeding on local rodents.
Item Type: | Journal Article | ||||
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Subjects: | Q Science > QR Microbiology > QR355 Virology | ||||
Divisions: | Faculty of Science, Engineering and Medicine > Science > Life Sciences (2010- ) | ||||
Library of Congress Subject Headings (LCSH): | DNA replication, Tick-borne encephalitis viruses -- Genetics | ||||
Journal or Publication Title: | Nucleic Acids Research | ||||
Publisher: | Oxford University Press | ||||
ISSN: | 0305-1048 | ||||
Official Date: | September 2011 | ||||
Dates: |
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Volume: | Vol.39 | ||||
Number: | No.16 | ||||
Page Range: | pp. 7034-7048 | ||||
DOI: | 10.1093/nar/gkr237 | ||||
Status: | Peer Reviewed | ||||
Publication Status: | Published | ||||
Access rights to Published version: | Restricted or Subscription Access | ||||
Date of first compliant deposit: | 18 December 2015 | ||||
Date of first compliant Open Access: | 18 December 2015 | ||||
Funder: | Biotechnology and Biological Sciences Research Council (Great Britain) (BBSRC), Sixth Framework Programme (European Commission) (FP6), Medical Research Council (Great Britain) (MRC) | ||||
Grant number: | BBS/B/00697 (BBSRC), LSHG-CT-2004-511960 (FP6), 87652 (MRC) |
Data sourced from Thomson Reuters' Web of Knowledge
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