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01-10-2017 | Brief Report

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

Authors: 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

Published in: Archives of Virology | Issue 10/2017

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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Title: Adaptation of tick-borne encephalitis virus from human brain to different cell cultures induces multiple genomic substitutions
Authors: 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
Publication date: 01-10-2017
Publisher: Springer Vienna
Published in: Archives of Virology / Issue 10/2017
Print ISSN: 0304-8608
Electronic ISSN: 1432-8798
DOI: https://doi.org/10.1007/s00705-017-3442-x

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