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Detection strategies of tick-borne encephalitis virus in Swedish Ixodes ricinus reveal evolutionary characteristics of emerging tick-borne flaviviruses.
Södertörn University, School of Life Sciences. Stockholm University.
Södertörn University, School of Life Sciences.
2007 (English)In: Archives of Virology, ISSN 0304-8608, E-ISSN 1432-8798, Vol. 152, no 5, 1027-1034 p.Article in journal (Refereed) Published
Abstract [en]

The flaviviral tick-borne encephalitis virus (TBEV) is a human pathogen having significant impact on public health. The geographical distribution of TBEV and TBEV-like viruses is increasing, which makes it important to characterise the natural virus populations. Here we present four RT-PCR strategies designed for detection of broad types of tick-borne flaviviruses. Sequence information on more than 32% of a TBEV genome was generated from a small pool of ticks collected in the Stockholm archipelago on the island of Torö. The sequences were characterised and compared with those of other tick-borne flaviviruses, which classified the virus as Western European TBEV.

Place, publisher, year, edition, pages
2007. Vol. 152, no 5, 1027-1034 p.
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:sh:diva-6063DOI: 10.1007/s00705-006-0922-9ISI: 000245965300018PubMedID: 17277902ScopusID: 2-s2.0-34247481383OAI: oai:DiVA.org:sh-6063DiVA: diva2:395524
Available from: 2011-02-07 Created: 2011-02-07 Last updated: 2014-03-10Bibliographically approved
In thesis
1. Molecular characterization of the Tick-borne encephalitis virus: Environments and replication
Open this publication in new window or tab >>Molecular characterization of the Tick-borne encephalitis virus: Environments and replication
2012 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

The flavivirus genus is of major concern for world morbidity and mortality and includes viruses causing both encephalitic as well as hemorrhagic diseases. The incidence of Tick-borne encephalitis is increasing in many European countries and several reports have emphasized the expansion of the main vector, Ixodes ricinus. The pattern of vector distribution is also changing in Sweden, which makes it important to set up solid and successful strategies for detection and genetic characterization of novel Swedish TBEV strains.

In this study we have generated strategies for detection of broad types of tick-borne flaviviruses in pools of I. ricinus sampled in Sweden.

The positive collection on the island of Torö was used to generate a sequence of a complete TBEV genome straight from the arthropod reservoir. This cloned virus was used to construct a self-replicating DNA based sub-genomic TBEV replicon capable of expressing reporter genes. The replicon was used to study the effect of TBEV on neurite outgrowth, which revealed that the MTase domain of NS5 block the formation of the Scribble/Rac1/βPIX protein complex, impairing neurite outgrowth in neuronal growth factor induced PC12 cells.

We also demonstrate that TBEV replication is affected by two PDZ binding motifs within NS5 and reveal putative PDZ binding proteins. These interactions might affect cellular pathways and might have a role in flavivirus replication.

We also characterize the variable 3´ non-coding region (V3’-NCR) by in silico studies on TBEV. Analysis brings new evidence that V3’-NCR region carries an enhancer element important for different replication/translation dynamics during the viral lifecycle in mammalian and tick cells. We also propose a temperature-sensitive trans-acting riboswitch mechanism; altering the secondary RNA structures of a closed form at lower temperatures and a form open for translation at higher temperatures. This mechanism may explain the low TBEV level observed in sampled ticks.

Place, publisher, year, edition, pages
Stockholm: Department of Genetics, Microbiology and Toxicology, Stockholm University, 2012. 71 p.
Series
Södertörn Doctoral Dissertations, ISSN 1652-7399 ; 63
Keyword
Tick-borne encephalitis virus
National Category
Biochemistry and Molecular Biology
Research subject
Molecular Genetics
Identifiers
urn:nbn:se:sh:diva-14829 (URN)978-91-7447-409-1 (ISBN)978-91-86069-42-1 (ISBN)
Public defence
2012-01-27, Magnélisalen, Kemiska övningslaboratoriet, Svante Arrhenius väg 16 B, 10:00 (English)
Opponent
Supervisors
Note

At the time of the doctoral defense, the following paper was unpublished and had a status as follows: Paper 4: Manuscript.

Available from: 2012-01-19 Created: 2012-01-19 Last updated: 2012-10-30Bibliographically approved

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