Inhibition of tick-borne encephalitis virus in cell cultures by ribavirin

Abstract

Tick-borne encephalitis virus (TBEV) belonging to arboviruses is a major member of zoonotic pathogens. TBEV infection causes severe human encephalitis without specific antiviral drugs. Due to its use of antiviral drug against a wide range of viruses, we investigated antiviral effect of ribavirin against TBEV in susceptible human cell lines A549 and SH-SY5Y. Ribavirin displayed minor cytotoxicity on multiple cell lines. Ribavirin obviously impaired TBEV replication and protected the infected cells from cytopathic effect. Importantly, ribavirin markedly inhibited TBEV propagation, as evidenced by impairment of TBEV production and viral RNA replication. Treatment with ribavirin (co-treatment and post-treatment) led to a dose-dependent reduction in TBEV titers as well as the viral RNA levels. Antiviral protein myxovirus resistance A mRNA expression was significantly up-regulated and signal transducer and activator of transcription 3 was activated in TBEV-infected A549 cells upon the ribavirin treatment. Induction of inflammatory cytokine tumor necrosis factor alpha by TBEV was decreased in A549 cells with the treatment of ribavirin, whereas interleukin 1 beta release appeared to be unaffected. These results suggest that ribavirin might represent a promising safe and effective antiviral drug against TBEV.

CD11b maintains West Nile virus replication through modulation of immune response in human neuroblastoma cells

“…Cells were cultured in Dulbecco’s modification of Eagle’s medium (Invitrogen, Carlsbad, USA) containing 10% fetal bovine serum, 1% L-glutamine, 1% non-essential amino acids, and 1% penicillin-streptomycin (complete medium) at 37 °C in a 5% CO 2 atmosphere. WNV and tick-borne encephalitis virus (TBEV) working stocks were prepared and titrated by plaque assay as described [ 19 , 20 ]. Experiments with virus infection were carried out in the Biological Safety Level 3 Laboratory in accordance with guidelines by the Committee on Safety of Biomedicine at Naval Medical University (Shanghai, China).…”

“…At 48 h post infection, SH-SY5Y cells with and without the siRNA transfection were assayed for cell viability using CellTiter 96 ® AQueous One Solution Cell Proliferation kit containing MTS (Promega, Madison, USA) following the manufacture’s instructions as described previously [ 19 ].…”

“…The primers used were listed in Supplementary Table S1 . The primers for TBEV and GAPDH were described previously [ 19 ].…”

Tick-Borne Encephalitis—Review of the Current Status

“…For example, nucleoside analogues have been investigated that can inhibit the RNA-dependent RNA polymerase or viral methyltransferases [99]. This group of compounds includes ribavirin, which interferes with TBEV replication and protects infected cells from cytopathic effects in cell culture [100]. Other strategies include human or chimeric monoclonal antibodies with the potential for post-exposure prophylaxis or early therapy [101].…”