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Title [en]
Molecular epidemiology, molecular evolution and vaccine development of Tick-borne encephalitis virus within the Baltic Sea region.
Abstract [en]
Tick-Borne Encephalitis virus (TBEV) cause severe CNS disease. Several factors, including climatechanges, have affected the TBEV distribution with significant outcome on the risks for human infections in the Baltic Sea region. TBEV can be subdivided into three subtypes, Western European (W-), Sibirian- (S-) and Far Eastern- (FE-) TBEV. The Baltic Sea region is an important study area as all three subtypes are present. Little is known about the molecular epidemiology of TBEV in Poland. As all the viral subtypes are co-circulating in the three Baltic States we believe that more virulent strains (S- and FE-) are present in northeast part of Poland, which calls for more profound TBEV studies within the region. Until recently, only W-TBEV has been detected in the Nordic countries, interestingly a recent report showed that the S-TBEV is abundantly present at the northern focus of Kokkola Finland. As e.g. birds can transport ticks over the Baltic Sea we hypothesise that S-TBEV could also be present at the corresponding Swedish latitude e.g. the Umeå area. This project will explore novel TBEV foci in northeast Sweden and northeast Poland with emphasis of the putative presence of S- and FE- TBEV. In addition, it was recently proposed that diversity in TBEV virulence is due to the presence of viral quasi-species within the tick reservoir. We have cloned a complete W-TBEV genome from ticks collected in the Baltic-Sea region. This will be used to construct a TBEV infectious cDNA clone. The clone would provide an intact virus free of ”quasi-species”. Studies on the virus evolution will be performed by passaging this virus in three different ways; strictly through tick cells, mammalian cells or alternating between the two cell types. Sequences from evolved viruses will give important data on essential genomic parts for respective host. The outcome will acquire knowledge on genetics, viral evolution and molecular mechanism underlaying the TBEV pathogenesis. Our recent work on molecular immune response to TBEV particularly viral protein NS5, will be used to introduce mutations in an infectious cDNA clone creating putative novel TBEV vaccine candidates. In addition, we are currently developing putative TBEV vaccine candidates based on the structural proteins expressed in plants in collaboration with Örebro University and Smittskyddsinstitutet. Improved TBEV vaccines will have great impact on future prevention strategies against TBEV in the Baltic-Sea region.
Publications (2 of 2) Show all publications
Asghar, N., Pettersson, J.-O. H., Dinnétz, P., Andreassen, Å. & Johansson, M. (2017). Deep sequencing analysis of tick-borne encephalitis virus from questing ticks at natural foci reveals similarities between quasispecies pools of the virus. Journal of General Virology, 98(3), 413-421
Open this publication in new window or tab >>Deep sequencing analysis of tick-borne encephalitis virus from questing ticks at natural foci reveals similarities between quasispecies pools of the virus
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2017 (English)In: Journal of General Virology, ISSN 0022-1317, E-ISSN 1465-2099, Vol. 98, no 3, p. 413-421Article in journal (Refereed) Published
Abstract [en]

Every year, tick-borne encephalitis virus (TBEV) causes severe central nervous system infection in 10 000 to 15 000 people in Europe and Asia. TBEV is maintained in the environment by an enzootic cycle that requires a tick vector and a vertebrate host, and the adaptation of TBEV to vertebrate and invertebrate environments is essential for TBEV persistence in nature. This adaptation is facilitated by the error-prone nature of the virus's RNA-dependent RNA polymerase, which generates genetically distinct virus variants called quasispecies. TBEV shows a focal geographical distribution pattern where each focus represents a TBEV hotspot. Here, we sequenced and characterized two TBEV genomes, JP-296 and JP-554, from questing Ixodes ricinus ticks at a TBEV focus in central Sweden. Phylogenetic analysis showed geographical clustering among the newly sequenced strains and three previously sequenced Scandinavian strains, Toro-2003, Saringe-2009 and Mandal-2009, which originated from the same ancestor. Among these five Scandinavian TBEV strains, only Mandal-2009 showed a large deletion within the 3' non-coding region (NCR), similar to the highly virulent TBEV strain Hypr. Deep sequencing of JP-296, JP-554 and Mandal-2009 revealed significantly high quasispecies diversity for JP-296 and JP-554, with intact 3' NCRs, compared to the low diversity in Mandal-2009, with a truncated 3' NCR. Single-nucleotide polymorphism analysis showed that 40% of the single-nucleotide polymorphisms were common between quasispecies populations of JP-296 and JP-554, indicating a putative mechanism for how TBEV persists and is maintained within its natural foci.

Place, publisher, year, edition, pages
The Microbiology Society, 2017
Keywords
:Ixodes ricinus; natural foci; non-coding region; quasispecies; Scandinavia; tick-borne encephalitis virus
National Category
Biological Sciences Environmental Sciences
Research subject
Environmental Studies; Baltic and East European studies
Identifiers
urn:nbn:se:sh:diva-31158 (URN)10.1099/jgv.0.000704 (DOI)000399235600013 ()28073402 (PubMedID)2-s2.0-85016952345 (Scopus ID)1330/42/2010 (Local ID)1330/42/2010 (Archive number)1330/42/2010 (OAI)
Funder
The Foundation for Baltic and East European Studies, A046-2010
Note

Som manuskript i avhandling. As manuscript in dissertation.

Available from: 2016-11-16 Created: 2016-11-16 Last updated: 2022-07-04Bibliographically approved
Bertrand, Y. J., Johansson, M. & Norberg, P. (2016). Revisiting Recombination Signal in the Tick-Borne Encephalitis Virus: A Simulation Approach. PLOS ONE, 11(10), Article ID e0164435.
Open this publication in new window or tab >>Revisiting Recombination Signal in the Tick-Borne Encephalitis Virus: A Simulation Approach
2016 (English)In: PLOS ONE, E-ISSN 1932-6203, Vol. 11, no 10, article id e0164435Article in journal (Refereed) Published
Abstract [en]

The hypothesis of wide spread reticulate evolution in Tick-Borne Encephalitis virus (TBEV) has recently gained momentum with several publications describing past recombination events involving various TBEV clades. Despite a large body of work, no consensus has yet emerged on TBEV evolutionary dynamics. Understanding the occurrence and frequency of recombination in TBEV bears significant impact on epidemiology, evolution, and vaccination with live vaccines. In this study, we investigated the possibility of detecting recombination events in TBEV by simulating recombinations at several locations on the virus' phylogenetic tree and for different lengths of recombining fragments. We derived estimations of rates of true and false positive for the detection of past recombination events for seven recombination detection algorithms. Our analytical framework can be applied to any investigation dealing with the difficult task of distinguishing genuine recombination signal from background noise. Our results suggest that the problem of false positives associated with low detection P-values in TBEV, is more insidious than generally acknowledged. We reappraised the recombination signals present in the empirical data, and showed that reliable signals could only be obtained in a few cases when highly genetically divergent strains were involved, whereas false positives were common among genetically similar strains. We thus conclude that recombination among wild-type TBEV strains may occur, which has potential implications for vaccination with live vaccines, but that these events are surprisingly rare.

National Category
Biological Sciences
Research subject
Baltic and East European studies
Identifiers
urn:nbn:se:sh:diva-31079 (URN)10.1371/journal.pone.0164435 (DOI)000386204000036 ()27760182 (PubMedID)2-s2.0-84992395862 (Scopus ID)
Funder
The Foundation for Baltic and East European Studies, A046-2010Knowledge Foundation, 20150201
Available from: 2016-11-03 Created: 2016-11-03 Last updated: 2022-07-04Bibliographically approved
Principal InvestigatorJohansson, Magnus
Co-InvestigatorElväng, Annelie
Coordinating organisation
Södertörn University
Funder
Period
2011-01-01 - 2013-12-31
Keywords [sv]
Östersjö- och Östeuropaforskning
Keywords [en]
Baltic and East European studies
National Category
Biochemistry and Molecular BiologyEnvironmental Sciences
Identifiers
DiVA, id: project:1836Project, id: A046-2010_OSS

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