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Dating the origin of the genus Flavivirus in the light of Beringian biogeography
Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Organismal Biology, Systematic Biology.
Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Organismal Biology, Systematic Biology.
2014 (English)In: Journal of General Virology, ISSN 0022-1317, E-ISSN 1465-2099, Vol. 95, 1969-1982 p.Article in journal (Refereed) Published
Abstract [en]

The genus Flavivirus includes some of the most important human viral pathogens, and itsmembers are found in all parts of the populated world. The temporal origin of diversification of thegenus has long been debated due to the inherent problems with dating deep RNA virus evolution.A generally accepted hypothesis suggests that Flavivirus emerged within the last 10 000 years.However, it has been argued that the tick-borne Powassan flavivirus was introduced into NorthAmerica some time between the opening and closing of the Beringian land bridge that connectedAsia and North America 15 000–11 000 years ago, indicating an even older origin for Flavivirus.To determine the temporal origin of Flavivirus, we performed Bayesian relaxed molecular clockdating on a dataset with high coverage of the presently available Flavivirus diversity by combiningtip date calibrations and internal node calibration, based on the Powassan virus and Beringianland bridge biogeographical event. Our analysis suggested that Flavivirus originated ~85 000(64 000–110 000) or 120 000 (87 000–159 000) years ago, depending on the circumscriptionof the genus. This is significantly older than estimated previously. In light of our results, wepropose that it is likely that modern humans came in contact with several members of the genusFlavivirus much earlier than suggested previously, and that it is possible that the spread of severalflaviviruses coincided with, and was facilitated by, the migration and population expansion ofmodern humans out of Africa.

Place, publisher, year, edition, pages
2014. Vol. 95, 1969-1982 p.
Keyword [en]
Flavivirus, virus evolution, virus dating, Beringia, POWV, molecular clock, molecular dating
National Category
Biological Systematics Microbiology
URN: urn:nbn:se:uu:diva-210860DOI: 10.1099/vir.0.065227-0ISI: 000341800500012PubMedID: 24914065OAI: oai:DiVA.org:uu-210860DiVA: diva2:665316
Available from: 2013-11-19 Created: 2013-11-15 Last updated: 2014-10-29Bibliographically approved
In thesis
1. The Origin of the Genus Flavivirus and the Ecology of Tick-Borne Pathogens
Open this publication in new window or tab >>The Origin of the Genus Flavivirus and the Ecology of Tick-Borne Pathogens
2013 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

The present thesis examines questions related to the temporal origin of the Flavivirus genus and the ecology of tick-borne pathogens. In the first study, we date the origin and divergence time of the Flavivirus genus. It has been argued that the first flaviviruses originated after the last glacial maximum. This has been contradicted by recent analyses estimating that the tick-borne flaviviruses emerged at least before 16,000 years ago. It has also been argued that the Powassan virus was introduced into North America at the time between the opening and splitting of the Beringian land bridge. Supported by tip date and biogeographical calibration, our results suggest that this genus originated circa 120,000 (156,100–322,700) years ago if the Tamana bat virus is included in the genus, or circa 85,000 (63,700–109,600) years ago excluding the Tamana bat virus. In the second study we estimate the prevalence of tick-borne encephalitis virus (TBEV) in host-seeking Ixodes ricinus from 29 localities in Sweden and compare our data with those of neighbouring countries. Nymphs and adult ticks were screened for TBEV using a real-time PCR assay. The mean TBEV prevalence for all tick stages combined was 0.26% for Sweden and 0.28% for all Scandinavian countries, excluding Iceland. The low prevalence of TBEV in nature may partly be explained by the fact that TBEV occurs in spatially small foci and that the inclusion of ticks from non-infected foci will reduce the prevalence estimate. In the third and fourth study, we conducted the first large-scale investigations to estimate the prevalence and geographical distribution of Anaplasma spp. and Rickettsia spp. in host-seeking larvae, nymphs and adults of I. ricinus ticks in Sweden. Ticks were collected from several localities in central and southern Sweden and were subsequently screened for the presence of Anaplasma spp. and Rickettsia spp. using a real-time PCR assay. For all active tick stages combined, the mean prevalence of Anaplasma spp. and Rickettsia spp. in I. ricinus in Sweden was estimated to 1.1% and 4.8%, respectively. It was also shown that A. phagocytophilum and R. helvetica are the main Anaplasma and Rickettsia species occurring in Sweden.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2013. 60 p.
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Science and Technology, ISSN 1651-6214 ; 1100
Flavivirus, Virus dating, Molecular dating, Biogeography, Ixodes ricinus, Minimum infection rate, TBE, Tick-borne encephalitis virus, Rickettsia helvetica, Anaplasma phagocytophilum, Infection prevalence, RT-PCR
National Category
Biological Sciences
Research subject
Biology with specialization in Systematics
urn:nbn:se:uu:diva-211090 (URN)978-91-554-8814-7 (ISBN)
Public defence
2014-01-10, Zootissalen, EBC, Villavägen 9, Uppsala, 13:00 (English)
Available from: 2013-12-10 Created: 2013-11-19 Last updated: 2014-01-24

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