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Adaptation of tick-borne encephalitis virus from human brain to different cell cultures induces multiple genomic substitutions

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Abstract

The C11-13 strain from the Siberian subtype of tick-borne encephalitis virus (TBEV) was isolated from human brain using pig embryo kidney (PEK), 293, and Neuro-2a cells. Analysis of the complete viral genome of the C11-13 variants during six passages in these cells revealed that the cell-adapted C11-13 variants had multiple amino acid substitutions as compared to TBEV from human brain. Seven out of eight amino acids substitutions in the high-replicating C11-13(PEK) variant mapped to non-structural proteins; 13 out of 14 substitutions in the well-replicating C11-13(293) variant, and all four substitutions in the low-replicating C11-13(Neuro-2a) variant were also localized in non-structural proteins, predominantly in the NS2a (2), NS3 (6) and NS5 (3) proteins. The substitutions NS2a1067 (Asn → Asp), NS2a1168(Leu → Val) in the N-terminus of NS2a and NS31745(His → Gln) in the helicase domain of NS3 were found in all selected variants. We postulate that multiple substitutions in the NS2a, NS3 and NS5 genes play a key role in adaptation of TBEV to different cells.

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Acknowledgements

This study was supported by the Russian Federal Service for Surveillance on Consumer Rights Protection and Human Wellbeing, Federal Target Program “Scientific Potential of Higher Schools”, and the Russian Fundamental Basic Investigation Agency.

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Authors and Affiliations

  1. Department of Molecular Virology for Flaviviruses and Viral Hepatitis, State Research Center for Virology and Biotechnology “Vector”, Koltsovo, Novosibirsk region, 630559, Russia

    Eugenia P. Ponomareva, Vladimir A. Ternovoi, Tamara P. Mikryukova, Elena V. Protopopova, Anastasia V. Gladysheva, Alexander N. Shvalov, Svetlana N. Konovalova, Eugene V. Chausov & Valery B. Loktev

  2. Tomsk State University, Tomsk, 634050, Russia

    Vladimir A. Ternovoi, Tamara P. Mikryukova, Elena V. Protopopova & Valery B. Loktev

  3. Institute of Cytology and Genetics, Novosibirsk, 630090, Russia

    Valery B. Loktev

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  1. Eugenia P. Ponomareva
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  2. Vladimir A. Ternovoi
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  3. Tamara P. Mikryukova
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  4. Elena V. Protopopova
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  5. Anastasia V. Gladysheva
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  6. Alexander N. Shvalov
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  7. Svetlana N. Konovalova
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  8. Eugene V. Chausov
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  9. Valery B. Loktev
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Correspondence to Valery B. Loktev.

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Ponomareva, E.P., Ternovoi, V.A., Mikryukova, T.P. et al. Adaptation of tick-borne encephalitis virus from human brain to different cell cultures induces multiple genomic substitutions. Arch Virol 162, 3151–3156 (2017). https://doi.org/10.1007/s00705-017-3442-x

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  • DOI: https://doi.org/10.1007/s00705-017-3442-x

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