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

作者：Ponomareva Eugenia P; Ternovoi Vladimir A; Mikryukova Tamara P; Protopopova Elena V; Gladysheva Anastasia V; Shvalov Alexander N; Konovalova Svetlana N; Chausov Eugene V; Loktev Valery B

来源：Archives of Virology, 2017, 162(10): 3151-3156.

DOI：10.1007/s00705-017-3442-x

• Tick-borne encephalitis virus
• Human brain
• Cells
• Genome substitutions

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 NS2a(1067) (Asn -> Asp), NS2a(1168)(Leu -> Val) in the N-terminus of NS2a and NS3(1745)(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.

• 出版日期2017-10