Tick-Borne Encephalitis Virus Nonstructural Protein NS5 Induces RANTES Expression Dependent on the RNA-Dependent RNA Polymerase Activity

The Journal of Immunology : Official Journal of the American Association of Immunologists
Zifeng ZhengQinxue Hu

Abstract

Tick-borne encephalitis virus (TBEV) is one of the flaviviruses that targets the CNS and causes encephalitis in humans. The mechanism of TBEV that causes CNS destruction remains unclear. It has been reported that RANTES-mediated migration of human blood monocytes and T lymphocytes is specifically induced in the brain of mice infected with TBEV, which causes ensuing neuroinflammation and may contribute to brain destruction. However, the viral components responsible for RANTES induction and the underlying mechanisms remain to be fully addressed. In this study, we demonstrate that the NS5, but not other viral proteins of TBEV, induces RANTES production in human glioblastoma cell lines and primary astrocytes. TBEV NS5 appears to activate the IFN regulatory factor 3 (IRF-3) signaling pathway in a manner dependent on RIG-I/MDA5, which leads to the nuclear translocation of IRF-3 to bind with RANTES promoter. Further studies reveal that the activity of RNA-dependent RNA polymerase (RdRP) but not the RNA cap methyltransferase is critical for TBEV NS5-induced RANTES expression, and this is likely due to RdRP-mediated synthesis of dsRNA. Additional data indicate that the residues at K359, D361, and D664 of TBEV NS5 are critical for RdRP a...Continue Reading

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Citations

Apr 19, 2020·Current Opinion in Neurology·Shenjian Ai, Robyn S Klein
Mar 27, 2020·Frontiers in Microbiology·Mei LiQinxue Hu
Oct 6, 2020·Frontiers in Immunology·Ritu Mishra, Akhil C Banerjea
Feb 28, 2021·Cellular & Molecular Immunology·Wenjing WangJianwei Wang
Jul 29, 2019·Neuroimmunomodulation·Rituraj NiranjanPurushothaman Jambulingam

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