Analysis of changes in the genome of the Omsk hemorrhagic fever virus (Flaviviridae: <i>Orthoflavivirus</i>) during laboratory practices for virus preservation

Introduction. Omsk hemorrhagic fever (OHF) is a severe disease identified in the 1940s in Western Siberia, Russia. Disease is caused by the OHF virus, which belongs to the genus Orthoflavivirus. The purpose of the work. Analysis of changes in the genome associated with the isolation of OHF virus...

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Main Authors: Zhanna S. Tyulko, Artem V. Fadeev, Aleksei G. Vasilenko, Ekaterina A. Gradoboeva, Valerii V. Yakimenko, Andrey B. Komissarov
Format: Article
Language:English
Published: Central Research Institute for Epidemiology 2024-12-01
Series:Вопросы вирусологии
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Online Access:https://virusjour.crie.ru/jour/article/viewFile/16686/944
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author Zhanna S. Tyulko
Artem V. Fadeev
Aleksei G. Vasilenko
Ekaterina A. Gradoboeva
Valerii V. Yakimenko
Andrey B. Komissarov
author_facet Zhanna S. Tyulko
Artem V. Fadeev
Aleksei G. Vasilenko
Ekaterina A. Gradoboeva
Valerii V. Yakimenko
Andrey B. Komissarov
author_sort Zhanna S. Tyulko
collection DOAJ
description Introduction. Omsk hemorrhagic fever (OHF) is a severe disease identified in the 1940s in Western Siberia, Russia. Disease is caused by the OHF virus, which belongs to the genus Orthoflavivirus. The purpose of the work. Analysis of changes in the genome associated with the isolation of OHF virus strains in laboratory animals (Mus musculus). Materials and methods. Whole-genome nucleotide sequences of OHF virus strains from the working collection of the laboratory of arboviral infections of the department of natural focal viral infections of the Omsk Research Institute of Natural Focal Infections of Rospotrebnadzor were used in the study, as well as sequences from GenBank. Assessment of adaptive changes in the genome of the OHF virus was carried out using discriminant analysis methods, analyzing the composition and localization of emerging substitutions in viral RNA sequences obtained during the adaptation of viruses to the mouse organism as a result of passaging. Linked nucleotide substitutions were identified by calculating the mutual information for each pair of columns in the array of aligned nucleotide sequences. In the phylogenetic analysis, the relaxed clock algorithm of the BEAST program was used. Results. It has been shown that point substitutions during adaptation of OHF viruses to the mouse organism occur in all parts of the genome. Many of these substitutions are included in the pattern of linked substitutions identified in the genome of the OHF virus. Discriminant analysis of differences in nucleotide substitutions for groups combining sequences by the number of passages does not allow reliable discrimination between original sequences obtained from muskrat and sequences from first passages, but it recognizes well sequences from 7 or more passages, which suggests the possibility of adaptive selection of nucleotide substitutions when interacting with the body of a white mouse. Calculation of the average rate of substitutions per site per year without taking into account the occurrence of adaptive and related substitutions gives a value of 10−5, which is almost an order of magnitude different from the result when their presence is taken into account ‒ 10−4. Conclusion. Changes in the nucleotide sequences of OHF that occur during laboratory virus preservation practices may influence the evolutionary rate values determined when analyzing these sequences and require further study.
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spelling doaj-art-a114d76a082143788793d39f694effa32025-01-22T15:18:43ZengCentral Research Institute for EpidemiologyВопросы вирусологии0507-40882411-20972024-12-0169650952310.36233/0507-4088-2661254Analysis of changes in the genome of the Omsk hemorrhagic fever virus (Flaviviridae: <i>Orthoflavivirus</i>) during laboratory practices for virus preservationZhanna S. Tyulko0https://orcid.org/0000-0001-8536-0520Artem V. Fadeev1https://orcid.org/0000-0003-3558-3261Aleksei G. Vasilenko2https://orcid.org/0000-0002-2754-6359Ekaterina A. Gradoboeva3https://orcid.org/0000-0002-2046-9872Valerii V. Yakimenko4https://orcid.org/0000-0001-9088-3668Andrey B. Komissarov5https://orcid.org/0000-0003-1733-1255Omsk Research Institute of Natural Focal Infections (Federal Service for Supervision of Consumer Rights Protection and Human Welfare)Smorodintsev Research Institute of Influenza, Ministry of Health of Russian FederationOmsk Research Institute of Natural Focal Infections (Federal Service for Supervision of Consumer Rights Protection and Human Welfare)Omsk Research Institute of Natural Focal Infections (Federal Service for Supervision of Consumer Rights Protection and Human Welfare)Omsk Research Institute of Natural Focal Infections (Federal Service for Supervision of Consumer Rights Protection and Human Welfare)Smorodintsev Research Institute of Influenza, Ministry of Health of Russian FederationIntroduction. Omsk hemorrhagic fever (OHF) is a severe disease identified in the 1940s in Western Siberia, Russia. Disease is caused by the OHF virus, which belongs to the genus Orthoflavivirus. The purpose of the work. Analysis of changes in the genome associated with the isolation of OHF virus strains in laboratory animals (Mus musculus). Materials and methods. Whole-genome nucleotide sequences of OHF virus strains from the working collection of the laboratory of arboviral infections of the department of natural focal viral infections of the Omsk Research Institute of Natural Focal Infections of Rospotrebnadzor were used in the study, as well as sequences from GenBank. Assessment of adaptive changes in the genome of the OHF virus was carried out using discriminant analysis methods, analyzing the composition and localization of emerging substitutions in viral RNA sequences obtained during the adaptation of viruses to the mouse organism as a result of passaging. Linked nucleotide substitutions were identified by calculating the mutual information for each pair of columns in the array of aligned nucleotide sequences. In the phylogenetic analysis, the relaxed clock algorithm of the BEAST program was used. Results. It has been shown that point substitutions during adaptation of OHF viruses to the mouse organism occur in all parts of the genome. Many of these substitutions are included in the pattern of linked substitutions identified in the genome of the OHF virus. Discriminant analysis of differences in nucleotide substitutions for groups combining sequences by the number of passages does not allow reliable discrimination between original sequences obtained from muskrat and sequences from first passages, but it recognizes well sequences from 7 or more passages, which suggests the possibility of adaptive selection of nucleotide substitutions when interacting with the body of a white mouse. Calculation of the average rate of substitutions per site per year without taking into account the occurrence of adaptive and related substitutions gives a value of 10−5, which is almost an order of magnitude different from the result when their presence is taken into account ‒ 10−4. Conclusion. Changes in the nucleotide sequences of OHF that occur during laboratory virus preservation practices may influence the evolutionary rate values determined when analyzing these sequences and require further study.https://virusjour.crie.ru/jour/article/viewFile/16686/944omsk hemorrhagic fever virusohf virus adaptation to the mouse organismdiscriminant analysislinked nucleotide substitutionsrate of substitutions occurrencephylogenetic analysis
spellingShingle Zhanna S. Tyulko
Artem V. Fadeev
Aleksei G. Vasilenko
Ekaterina A. Gradoboeva
Valerii V. Yakimenko
Andrey B. Komissarov
Analysis of changes in the genome of the Omsk hemorrhagic fever virus (Flaviviridae: <i>Orthoflavivirus</i>) during laboratory practices for virus preservation
Вопросы вирусологии
omsk hemorrhagic fever virus
ohf virus adaptation to the mouse organism
discriminant analysis
linked nucleotide substitutions
rate of substitutions occurrence
phylogenetic analysis
title Analysis of changes in the genome of the Omsk hemorrhagic fever virus (Flaviviridae: <i>Orthoflavivirus</i>) during laboratory practices for virus preservation
title_full Analysis of changes in the genome of the Omsk hemorrhagic fever virus (Flaviviridae: <i>Orthoflavivirus</i>) during laboratory practices for virus preservation
title_fullStr Analysis of changes in the genome of the Omsk hemorrhagic fever virus (Flaviviridae: <i>Orthoflavivirus</i>) during laboratory practices for virus preservation
title_full_unstemmed Analysis of changes in the genome of the Omsk hemorrhagic fever virus (Flaviviridae: <i>Orthoflavivirus</i>) during laboratory practices for virus preservation
title_short Analysis of changes in the genome of the Omsk hemorrhagic fever virus (Flaviviridae: <i>Orthoflavivirus</i>) during laboratory practices for virus preservation
title_sort analysis of changes in the genome of the omsk hemorrhagic fever virus flaviviridae i orthoflavivirus i during laboratory practices for virus preservation
topic omsk hemorrhagic fever virus
ohf virus adaptation to the mouse organism
discriminant analysis
linked nucleotide substitutions
rate of substitutions occurrence
phylogenetic analysis
url https://virusjour.crie.ru/jour/article/viewFile/16686/944
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