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Genomic Determinants Potentially Associated with Clinical Manifestations of Human-Pathogenic Tick-Borne Flaviviruses.
Bondaryuk, Artem N; Kulakova, Nina V; Potapova, Ulyana V; Belykh, Olga I; Yudinceva, Anzhelika V; Bukin, Yurij S.
Afiliación
  • Bondaryuk AN; Laboratory of Natural Focal Viral Infections, Irkutsk Antiplague Research Institute of Siberia and the Far East, 664047 Irkutsk, Russia.
  • Kulakova NV; Limnological Institute, Siberian Branch of the Russian Academy of Sciences, 664033 Irkutsk, Russia.
  • Potapova UV; Department of Biodiversity and Biological Resources, Siberian Institute of Plant Physiology and Biochemistry, Siberian Branch of the Russian Academy of Sciences, 664033 Irkutsk, Russia.
  • Belykh OI; Limnological Institute, Siberian Branch of the Russian Academy of Sciences, 664033 Irkutsk, Russia.
  • Yudinceva AV; Limnological Institute, Siberian Branch of the Russian Academy of Sciences, 664033 Irkutsk, Russia.
  • Bukin YS; Limnological Institute, Siberian Branch of the Russian Academy of Sciences, 664033 Irkutsk, Russia.
Int J Mol Sci ; 23(21)2022 Nov 02.
Article en En | MEDLINE | ID: mdl-36362200
The tick-borne flavivirus group contains at least five species that are pathogenic to humans, three of which induce encephalitis (tick-borne encephalitis virus, louping-ill virus, Powassan virus) and another two species induce hemorrhagic fever (Omsk hemorrhagic fever virus, Kyasanur Forest disease virus). To date, the molecular mechanisms responsible for these strikingly different clinical forms are not completely understood. Using a bioinformatic approach, we performed the analysis of each amino acid (aa) position in the alignment of 323 polyprotein sequences to calculate the fixation index (Fst) per site and find the regions (determinants) where sequences belonging to two designated groups were most different. Our algorithm revealed 36 potential determinants (Fst ranges from 0.91 to 1.0) located in all viral proteins except a capsid protein. In an envelope (E) protein, most of the determinants were located on the virion surface regions (domains II and III) and one (absolutely specific site 457) was located in the transmembrane region. Another 100% specific determinant site (E63D) with Fst = 1.0 was located in the central hydrophilic domain of the NS2b, which mediates NS3 protease activity. The NS5 protein contains the largest number of determinants (14) and two of them are absolutely specific (T226S, E290D) and are located near the RNA binding site 219 (methyltransferase domain) and the extension structure. We assume that even if not absolutely, highly specific sites, together with absolutely specific ones (Fst = 1.0) can play a supporting role in cell and tissue tropism determination.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Garrapatas / Virus de la Encefalitis Transmitidos por Garrapatas Tipo de estudio: Risk_factors_studies Límite: Animals / Humans Idioma: En Revista: Int J Mol Sci Año: 2022 Tipo del documento: Article País de afiliación: Rusia Pais de publicación: Suiza
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Garrapatas / Virus de la Encefalitis Transmitidos por Garrapatas Tipo de estudio: Risk_factors_studies Límite: Animals / Humans Idioma: En Revista: Int J Mol Sci Año: 2022 Tipo del documento: Article País de afiliación: Rusia Pais de publicación: Suiza