In vitro antiviral activity of ribavirin against severe fever with thrombocytopenia syndrome virus
2
조회
0
다운로드
4
인용
0
참고문헌
키워드
초록
Background/Aims: Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease caused by severe fever with thrombocytopenia syndrome virus (SFTSV), a novel bunyavirus. As yet, there is no effective antiviral therapy for SFTS. Ribavirin is a broad-spectrum antiviral agent, which has been tried for treatment of SFTS. In this study, antiviral activity of ribavirin against SFTSV has been investigated. Methods: Vero cell-grown SFTSV strain Gangwon/Korea/2012 was treated with ribavirin at various concentrations. Antiviral activity of ribavirin was evaluated by inhibition of the SFTSV cytopathic effect in Vero cells and quantification of viral RNA load in culture supernatant using one-step real-time reverse transcription polymerase chain reaction. Cytotoxicity of ribavirin was determined by a tetrazolium- based colorimetric method. Results: Ribavirin reduced SFTSV titers in a dose-dependent manner, with a half-maximal inhibitory concentration ranged from 3.69 to 8.72 μg/mL. Cytopathic effects were reduced as ribavirin concentration increased. No significant cytotoxicity was detected at ribavirin concentrations of ≤ 31.3 μg/mL. Conclusions: Ribavirin exhibited inhibitory activity against SFTSV replication in vitro, which suggests that ribavirin can be used as a potential antiviral agent for SFTS.
Abstract
Background/Aims: Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease caused by severe fever with thrombocytopenia syndrome virus (SFTSV), a novel bunyavirus. As yet, there is no effective antiviral therapy for SFTS. Ribavirin is a broad-spectrum antiviral agent, which has been tried for treatment of SFTS. In this study, antiviral activity of ribavirin against SFTSV has been investigated. Methods: Vero cell-grown SFTSV strain Gangwon/Korea/2012 was treated with ribavirin at various concentrations. Antiviral activity of ribavirin was evaluated by inhibition of the SFTSV cytopathic effect in Vero cells and quantification of viral RNA load in culture supernatant using one-step real-time reverse transcription polymerase chain reaction. Cytotoxicity of ribavirin was determined by a tetrazolium- based colorimetric method. Results: Ribavirin reduced SFTSV titers in a dose-dependent manner, with a half-maximal inhibitory concentration ranged from 3.69 to 8.72 μg/mL. Cytopathic effects were reduced as ribavirin concentration increased. No significant cytotoxicity was detected at ribavirin concentrations of ≤ 31.3 μg/mL. Conclusions: Ribavirin exhibited inhibitory activity against SFTSV replication in vitro, which suggests that ribavirin can be used as a potential antiviral agent for SFTS.
참고문헌 (21)
- Yu XJ, "Fever with thrombocytopenia associated with a novel bunyavirus in China", N Engl J Med, 364, pp.1523~1532 (2011)
- Takahashi T, "The first identification and retrospective study of severe fever with thrombocytopenia syndrome in Japan", J Infect Dis, 209, pp.816~827 (2014)
- Kim KH, "Severe fever with thrombocytopenia syndrome, South Korea, 2012", Emerg Infect Di, 19, pp.1892~1894 (2013)
- Liu W, "Case-fatality ratio and effectiveness of ribavirin therapy among hospitalized patients in china who had severe fever with thrombocytopenia syndrome", Clin Infect Dis, 57, pp.1292~1299 (2013)
- Huggins JW., "Prospects for treatment of viral hemorrhagic fevers with ribavirin, a broad-spectrum antiviral drug", Rev Infect Dis, 11(Suppl 4), pp.S750~S761 (1989)
- Rusnak JM., "Experience with ribavirin for treatment and postexposure prophylaxis of hemorrhagic fever viruses:Crimean Congo hemorrhagic fever, lassa fever, and hantaviruses", Appl Biosaf, 16, pp.67~87 (2011)
- Oh WS, "Plasma exchange and ribavirin for rapidly progressive severe fever with thrombocytopenia syndrome", Int J Infect Dis, 18, pp.84~86 (2014)
- Reed LJ, "A simple method of estimating fifty percent endpoints", Am J Epidemiol, 27, pp.493~497 (1938)
- Sun Y, "Early diagnosis of novel SFTS bunyavirus infection by quantitative real-time RT-PCR assay", J Clin Virol, 53, pp.48~53 (2012)
- Shimojima M, "Effects of ribavirin on severe fever with thrombocytopenia syndrome virus in vitro", Jpn J Infect Dis, 67, pp.423~427 (2014)
- Shah NR, "Cell type mediated resistance of vesicular stomatitis virus and Sendai virus to ribavirin", PLoS One, 5, pp.e11265~ (2010)
- Paragas J, "A simple assay for determining antiviral activity against Crimean-Congo hemorrhagic fever virus", Antiviral Res, 62, pp.21~25 (2004)
- Ozbey SB, "Early use of ribavirin is beneficial in Crimean-Congo hemorrhagic fever", Vector Borne Zoonotic Dis, 14, pp.300~302 (2014)
- Tasdelen Fisgin N, "The role of ribavirin in the therapy of Crimean-Congo hemorrhagic fever: early use is promising", Eur J Clin Microbiol Infect Dis, 28, pp.929~933 (2009)
- Toltzis P, "Effect of ribavirin on macromolecular synthesis in vesicular stomatitis virus-infected cells", Antimicrob Agents Chemother, 29, pp.1010~1016 (1986)
- Hruska JF, "Effects of ribavirin on respiratory syncytial virus in vitro", Antimicrob Agents Chemother, 17, pp.770~775 (1980)
- Sun Y, "Host cytokine storm is associated with disease severity of severe fever with thrombocytopenia syndrome", J Infect Dis, 206, pp.1085~1094 (2012)
- Fernandez H, "Ribavirin: a clinical overview", Eur J Epidemiol, 2, pp.1~14 (1986)
- Bausch DG, "Review of the literature and proposed guidelines for the use of oral ribavirin as postexposure prophylaxis for Lassa fever", Clin Infect Dis, 51, pp.1435~1441 (2010)
- Jin C, "Pathogenesis of emerging severe fever with thrombocytopenia syndrome virus in C57", BL6 mouse model, 2012, pp.109, 10053~10058
- Liu Y, "The pathogenesis of severe fever with thrombocytopenia syndrome virus infection in alpha", beta interferon knockout mice: insights into the pathologic mechanisms of a new viral hemorrhagic fever, 2014, pp.88, 1781~1786
