{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T02:20:17Z","timestamp":1760149217726,"version":"build-2065373602"},"reference-count":32,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2023,7,19]],"date-time":"2023-07-19T00:00:00Z","timestamp":1689724800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Limnological Institute, Siberian Branch of the Russian Academy of Sciences","award":["121032300196-8"],"award-info":[{"award-number":["121032300196-8"]}]},{"name":"Irkutsk Antiplague Research Institute of Siberia and the Far East","award":["121032300196-8"],"award-info":[{"award-number":["121032300196-8"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>Until 2020, there were only three original complete genome (CG) nucleotide sequences of Omsk hemorrhagic fever virus (OHFV) in GenBank. For this reason, the evolutionary rate and divergence time assessments reported in the literature were based on the E gene sequences, but notably without temporal signal evaluation, such that their reliability is unclear. As of July 2022, 47 OHFV CG sequences have been published, which enables testing of temporal signal in the data and inferring unbiased and reliable substitution rate and divergence time values. Regression analysis in the TempEst software demonstrated a stronger clocklike behavior in OHFV samples for the complete open reading frame (ORF) data set (R2 = 0.42) than for the E gene data set (R2 = 0.11). Bayesian evaluation of temporal signal indicated very strong evidence, with a log Bayes factor of more than 5, in favor of temporal signal in all data sets. Our results based on the complete ORF sequences showed a more precise OHFV substitution rate (95% highest posterior density (HPD) interval, 9.1 \u00d7 10\u22125\u20131.8 \u00d7 10\u22124 substitutions per site per year) and tree root height (416\u2013896 years ago) compared with previous assessments. The rate obtained is significantly higher than tick-borne encephalitis virus by at least 3.8-fold. The phylogenetic analysis and past population dynamics reconstruction revealed the declining trend of OHFV genetic diversity, but there was phylogenomic evidence that implicit virus subpopulations evolved locally and underwent an exponential growth phase.<\/jats:p>","DOI":"10.3390\/v15071576","type":"journal-article","created":{"date-parts":[[2023,7,19]],"date-time":"2023-07-19T21:20:14Z","timestamp":1689801614000},"page":"1576","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Inferring Evolutionary Timescale of Omsk Hemorrhagic Fever Virus"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4422-0497","authenticated-orcid":false,"given":"Artem N.","family":"Bondaryuk","sequence":"first","affiliation":[{"name":"Laboratory of Natural Focal Viral Infections, Irkutsk Antiplague Research Institute of Siberia and the Far East, Irkutsk 664047, Russia"},{"name":"Limnological Institute, Siberian Branch of the Russian Academy of Sciences, Irkutsk 664033, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1188-7351","authenticated-orcid":false,"given":"Olga I.","family":"Belykh","sequence":"additional","affiliation":[{"name":"Limnological Institute, Siberian Branch of the Russian Academy of Sciences, Irkutsk 664033, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Evgeny I.","family":"Andaev","sequence":"additional","affiliation":[{"name":"Laboratory of Natural Focal Viral Infections, Irkutsk Antiplague Research Institute of Siberia and the Far East, Irkutsk 664047, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4534-3846","authenticated-orcid":false,"given":"Yurij S.","family":"Bukin","sequence":"additional","affiliation":[{"name":"Limnological Institute, Siberian Branch of the Russian Academy of Sciences, Irkutsk 664033, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,7,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"39","DOI":"10.31631\/2073-3046-2015-14-1-39-48","article-title":"Epidemiology of Omsk Haemorragic Fever","volume":"14","author":"Rudakov","year":"2015","journal-title":"Epidemiol. Vaccine Prev."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"101627","DOI":"10.1016\/j.ttbdis.2020.101627","article-title":"Molecular variability and genetic structure of Omsk hemorrhagic fever virus, based on analysis of the complete genome sequences","volume":"12","author":"Kovalev","year":"2021","journal-title":"Ticks Tick. Borne Dis."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1181","DOI":"10.1002\/jmv.23856","article-title":"The deduced evolution history of Omsk hemorrhagic fever virus","volume":"86","author":"Karan","year":"2014","journal-title":"J. Med. Virol."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Wagner, E., Shin, A., Tukhanova, N., Turebekov, N., Nurmakhanov, T., Sutyagin, V., Berdibekov, A., Maikanov, N., Lezdinsh, I., and Shapiyeva, Z. (2022). First Indications of Omsk Haemorrhagic Fever Virus beyond Russia. Viruses, 14.","DOI":"10.3390\/v14040754"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"520","DOI":"10.32614\/RJ-2017-058","article-title":"rentrez: An R package for the NCBI eUtils API","volume":"9","author":"Winter","year":"2017","journal-title":"R J."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"vew007","DOI":"10.1093\/ve\/vew007","article-title":"Exploring the temporal structure of heterochronous sequences using TempEst (formerly Path-O-Gen)","volume":"2","author":"Rambaut","year":"2016","journal-title":"Virus Evol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"3363","DOI":"10.1093\/molbev\/msaa163","article-title":"Bayesian Evaluation of Temporal Signal in Measurably Evolving Populations","volume":"37","author":"Duchene","year":"2020","journal-title":"Mol. Biol. Evol."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Bouckaert, R., Vaughan, T.G., Barido-Sottani, J., Duchene, S., Fourment, M., Gavryushkina, A., Heled, J., Jones, G., Kuhnert, D., and De Maio, N. (2019). BEAST 2.5: An advanced software platform for Bayesian evolutionary analysis. PLoS Comput. Biol., 15.","DOI":"10.1371\/journal.pcbi.1006650"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"268","DOI":"10.1093\/molbev\/msu300","article-title":"IQ-TREE: A fast and effective stochastic algorithm for estimating maximum-likelihood phylogenies","volume":"32","author":"Nguyen","year":"2015","journal-title":"Mol. Biol. Evol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"587","DOI":"10.1038\/nmeth.4285","article-title":"ModelFinder: Fast model selection for accurate phylogenetic estimates","volume":"14","author":"Kalyaanamoorthy","year":"2017","journal-title":"Nat. Methods"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1185","DOI":"10.1093\/molbev\/msi103","article-title":"Bayesian coalescent inference of past population dynamics from molecular sequences","volume":"22","author":"Drummond","year":"2005","journal-title":"Mol. Biol. Evol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1111\/2041-210X.12466","article-title":"The effect of genetic structure on molecular dating and tests for temporal signal","volume":"7","author":"Murray","year":"2016","journal-title":"Methods Ecol. Evol."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Heller, R., Chikhi, L., and Siegismund, H.R. (2013). The confounding effect of population structure on Bayesian skyline plot inferences of demographic history. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0062992"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1879","DOI":"10.1098\/rstb.2010.0060","article-title":"Viral phylodynamics and the search for an \u2018effective number of infections\u2019","volume":"365","author":"Frost","year":"2010","journal-title":"Philos. Trans. R. Soc. B Biol. Sci."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"2104","DOI":"10.1016\/S0140-6736(10)61120-8","article-title":"Omsk haemorrhagic fever","volume":"376","author":"Ruzek","year":"2010","journal-title":"Lancet"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1111\/j.1755-0998.2011.02988.x","article-title":"Skyline-plot methods for estimating demographic history from nucleotide sequences","volume":"11","author":"Ho","year":"2011","journal-title":"Mol. Ecol. Resour."},{"key":"ref_17","first-page":"20140732","article-title":"Analyses of evolutionary dynamics in viruses are hindered by a time-dependent bias in rate estimates","volume":"281","author":"Duchene","year":"2014","journal-title":"Proc. Biol. Sci."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"e01031-17","DOI":"10.1128\/JVI.01031-17","article-title":"Complexities of Viral Mutation Rates","volume":"92","author":"Peck","year":"2018","journal-title":"J. Virol."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Bondaryuk, A.N., Kulakova, N.V., Belykh, O.I., and Bukin, Y.S. (2023). Dates and Rates of Tick-Borne Encephalitis Virus-The Slowest Changing Tick-Borne Flavivirus. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24032921"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Bondaryuk, A.N., Peretolchina, T.E., Romanova, E.V., Yudinceva, A.V., Andaev, E.I., and Bukin, Y.S. (2021). Phylogeography and Re-Evaluation of Evolutionary Rate of Powassan Virus Using Complete Genome Data. Biology, 10.","DOI":"10.3390\/biology10121282"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"e2218012120","DOI":"10.1073\/pnas.2218012120","article-title":"Phylogeographic reconstruction of the emergence and spread of Powassan virus in the northeastern United States","volume":"120","author":"Vogels","year":"2023","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"vead008","DOI":"10.1093\/ve\/vead008","article-title":"Phylodynamics of deer tick virus in North America","volume":"9","author":"McMinn","year":"2023","journal-title":"Virus Evol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1966","DOI":"10.1038\/s41598-020-58242-w","article-title":"Phylogeography of Kyasanur Forest Disease virus in India (1957-2017) reveals evolution and spread in the Western Ghats region","volume":"10","author":"Yadav","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Dodd, K.A., Bird, B.H., Khristova, M.L., Albarino, C.G., Carroll, S.A., Comer, J.A., Erickson, B.R., Rollin, P.E., and Nichol, S.T. (2011). Ancient ancestry of KFDV and AHFV revealed by complete genome analyses of viruses isolated from ticks and mammalian hosts. PLoS Negl. Trop. Dis., 5.","DOI":"10.1371\/journal.pntd.0001352"},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Clark, J.J., Gilray, J., Orton, R.J., Baird, M., Wilkie, G., Filipe, A.D.S., Johnson, N., McInnes, C.J., Kohl, A., and Biek, R. (2020). Population genomics of louping ill virus provide new insights into the evolution of tick-borne flaviviruses. PLoS Negl. Trop. Dis., 14.","DOI":"10.1101\/2020.02.14.949230"},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Volz, E.M., Koelle, K., and Bedford, T. (2013). Viral phylodynamics. PLoS Comput. Biol., 9.","DOI":"10.1371\/journal.pcbi.1002947"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"786","DOI":"10.1099\/vir.0.035766-0","article-title":"Rate of evolution and molecular epidemiology of tick-borne encephalitis virus in Europe, including two isolations from the same focus 44 years apart","volume":"93","author":"Sironen","year":"2012","journal-title":"J. Gen. Virol."},{"key":"ref_28","unstructured":"Lavrov, N.P. (1957). Akklimatizatsiya Ondatry v SSSR, Tsentrsoyuz."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"224","DOI":"10.1016\/j.ttbdis.2015.10.015","article-title":"Geographical distribution of Dermacentor marginatus and Dermacentor reticulatus in Europe","volume":"7","author":"Rubel","year":"2016","journal-title":"Ticks Tick. Borne Dis."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Bondaryuk, A.N., Kulakova, N.V., Potapova, U.V., Belykh, O.I., Yudinceva, A.V., and Bukin, Y.S. (2022). Genomic Determinants Potentially Associated with Clinical Manifestations of Human-Pathogenic Tick-Borne Flaviviruses. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms232113404"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"2985","DOI":"10.1002\/ece3.685","article-title":"Coevolutionary analyses of the relationships between piroplasmids and their hard tick hosts","volume":"3","author":"Gou","year":"2013","journal-title":"Ecol. Evol."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Moureau, G., Cook, S., Lemey, P., Nougairede, A., Forrester, N.L., Khasnatinov, M., Charrel, R.N., Firth, A.E., Gould, E.A., and de Lamballerie, X. (2015). New insights into flavivirus evolution, taxonomy and biogeographic history, extended by analysis of canonical and alternative coding sequences. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0117849"}],"container-title":["Viruses"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4915\/15\/7\/1576\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T20:14:36Z","timestamp":1760127276000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4915\/15\/7\/1576"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,7,19]]},"references-count":32,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2023,7]]}},"alternative-id":["v15071576"],"URL":"https:\/\/doi.org\/10.3390\/v15071576","relation":{},"ISSN":["1999-4915"],"issn-type":[{"type":"electronic","value":"1999-4915"}],"subject":[],"published":{"date-parts":[[2023,7,19]]}}}