Effects of Ribavirin on Severe Fever with Thrombocytopenia Syndrome Virus In Vitro
Severe fever with thrombocytopenia syndrome (SFTS) is a disease with a high case fatality rate that is caused by infection with the recently identified tick-borne SFTS virus (SFTSV), for which there are no specific countermeasures. We examined the effects of ribavirin and mizoribine, which are nucle...
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| Published in | Japanese Journal of Infectious Diseases Vol. 67; no. 6; pp. 423 - 427 |
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| Main Authors | , , , , , , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
Japan
National Institute of Infectious Diseases, Japanese Journal of Infectious Diseases Editorial Committee
2014
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| Subjects | |
| Online Access | Get full text |
| ISSN | 1344-6304 1884-2836 1884-2836 |
| DOI | 10.7883/yoken.67.423 |
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| Abstract | Severe fever with thrombocytopenia syndrome (SFTS) is a disease with a high case fatality rate that is caused by infection with the recently identified tick-borne SFTS virus (SFTSV), for which there are no specific countermeasures. We examined the effects of ribavirin and mizoribine, which are nucleoside analogue drugs with broad antiviral activities, on SFTSV proliferation in vitro. When 3 cell lines were treated with these drugs before and during infection with a Chinese SFTSV strain, the 99% effective concentrations (EC99) of ribavirin were 19–64 μg/ml (78–262 μM); in contrast, the EC99 of mizoribine was >500 μg/ml (1,929 μM). Similar levels of inhibitory effects of ribavirin were observed with 4 Japanese SFTSV strains. However, when Vero cells were treated with ribavirin 3 days after inoculation, the inhibitory effect was dramatically decreased, indicating that ribavirin did not effectively reduce virus production in pre-infected cells. These results suggest that ribavirin could be used as post-exposure prophylaxis for the prevention of SFTS. |
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| AbstractList | Severe fever with thrombocytopenia syndrome (SFTS) is a disease with a high case fatality rate that is caused by infection with the recently identified tick-borne SFTS virus (SFTSV), for which there are no specific countermeasures. We examined the effects of ribavirin and mizoribine, which are nucleoside analogue drugs with broad antiviral activities, on SFTSV proliferation in vitro. When 3 cell lines were treated with these drugs before and during infection with a Chinese SFTSV strain, the 99% effective concentrations (EC99) of ribavirin were 19-64 μg/ml (78-262 μM); in contrast, the EC99 of mizoribine was >500 μg/ml (1,929 μM). Similar levels of inhibitory effects of ribavirin were observed with 4 Japanese SFTSV strains. However, when Vero cells were treated with ribavirin 3 days after inoculation, the inhibitory effect was dramatically decreased, indicating that ribavirin did not effectively reduce virus production in pre-infected cells. These results suggest that ribavirin could be used as post-exposure prophylaxis for the prevention of SFTS.Severe fever with thrombocytopenia syndrome (SFTS) is a disease with a high case fatality rate that is caused by infection with the recently identified tick-borne SFTS virus (SFTSV), for which there are no specific countermeasures. We examined the effects of ribavirin and mizoribine, which are nucleoside analogue drugs with broad antiviral activities, on SFTSV proliferation in vitro. When 3 cell lines were treated with these drugs before and during infection with a Chinese SFTSV strain, the 99% effective concentrations (EC99) of ribavirin were 19-64 μg/ml (78-262 μM); in contrast, the EC99 of mizoribine was >500 μg/ml (1,929 μM). Similar levels of inhibitory effects of ribavirin were observed with 4 Japanese SFTSV strains. However, when Vero cells were treated with ribavirin 3 days after inoculation, the inhibitory effect was dramatically decreased, indicating that ribavirin did not effectively reduce virus production in pre-infected cells. These results suggest that ribavirin could be used as post-exposure prophylaxis for the prevention of SFTS. Severe fever with thrombocytopenia syndrome (SFTS) is a disease with a high case fatality rate that is caused by infection with the recently identified tick-borne SFTS virus (SFTSV), for which there are no specific countermeasures. We examined the effects of ribavirin and mizoribine, which are nucleoside analogue drugs with broad antiviral activities, on SFTSV proliferation in vitro. When 3 cell lines were treated with these drugs before and during infection with a Chinese SFTSV strain, the 99% effective concentrations (EC99) of ribavirin were 19–64 μg/ml (78–262 μM); in contrast, the EC99 of mizoribine was >500 μg/ml (1,929 μM). Similar levels of inhibitory effects of ribavirin were observed with 4 Japanese SFTSV strains. However, when Vero cells were treated with ribavirin 3 days after inoculation, the inhibitory effect was dramatically decreased, indicating that ribavirin did not effectively reduce virus production in pre-infected cells. These results suggest that ribavirin could be used as post-exposure prophylaxis for the prevention of SFTS. |
| Author | Suda, Yuto Morikawa, Shigeru Shimojima, Masayuki Taniguchi, Satoshi Saijo, Masayuki Takahashi, Toru Fukuma, Aiko Fukushi, Shuetsu Tani, Hideki Yoshikawa, Tomoki Maeda, Ken |
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| References | 5. Takahashi T, Maeda K, Suzuki T, et al. The first identification and retrospective study of severe fever with thrombocytopenia syndrome in Japan. J Infect Dis. 2014;209:816-27. 11. Tang X, Wu W, Wang H, et al. Human-to-human transmission of severe fever with thrombocytopenia syndrome bunyavirus through contact with infectious blood. J Infect Dis. 2013;207:736-9. 13. Lange CM, Jacobson IM, Rice CM, et al. Emerging therapies for the treatment of hepatitis C. EMBO Mol Med. 2014;6:4-15. 9. Gai Z, Liang M, Zhang Y, et al. Person-to-person transmission of severe fever with thrombocytopenia syndrome bunyavirus through blood contact. Clin Infect Dis. 2012;54:249-52. 26. Yokota S. Mizoribine: mode of action and effects in clinical use. Pediatr Int. 2002;44:196-8. 23. Peters CJ, Reynolds JA, Slone TW, et al. Prophylaxis of Rift Valley fever with antiviral drugs, immune serum, an interferon inducer, and a macrophage activator. Antiviral Res. 1986;6:285-97. 31. Zhang YZ, He YW, Dai YA, et al. Hemorrhagic fever caused by a novel Bunyavirus in China: pathogenesis and correlates of fatal outcome. Clin Infect Dis. 2012;54:527-33. 30. Sun Y, Jin C, Zhan F, et al. Host cytokine storm is associated with disease severity of severe fever with thrombocytopenia syndrome. J Infect Dis. 2012;206:1085-94. 14. Keshtkar-Jahromi M, Kuhn JH, Christova I, et al. Crimean-Congo hemorrhagic fever: current and future prospects of vaccines and therapies. Antiviral Res. 2011;90:85-92. 24. Reed C, Lin K, Wilhelmsen C, et al. Aerosol exposure to Rift Valley fever virus causes earlier and more severe neuropathology in the murine model, which has important implications for therapeutic development. PLoS Negl Trop Dis. 2013;7:e2156. 8. Bao CJ, Guo XL, Qi X, et al. A family cluster of infections by a newly recognized bunyavirus in eastern China, 2007: further evidence of person-to-person transmission. Clin Infect Dis. 2011;53:1208-14. 16. Li S, Xue C, Fu Y, et al. Sporadic case infected by severe fever with thrombocytopenia syndrome bunyavirus in a non-epidemic region of China. Biosci Trends. 2011;5:273-6. 33. Lanford RE, Guerra B, Lee H, et al. Antiviral effect and virus-host interactions in response to alpha interferon, gamma interferon, poly(I)-poly(C), tumor necrosis factor alpha, and ribavirin in hepatitis C virus subgenomic replicons. J Virol. 2003;77:1092-104. 32. Liu W, Lu QB, Cui N, et al. Case-fatality ratio and effectiveness of ribavirin therapy among hospitalized patients in China who had severe fever with thrombocytopenia syndrome. Clin Infect Dis. 2013;57:1292-9. 18. Shigeta S. Recent progress in antiviral chemotherapy for respiratory syncytial virus infections. Expert Opin Investig Drugs. 2000;9:221-35. 2. Xu B, Liu L, Huang X, et al. Metagenomic analysis of fever, thrombocytopenia and leukopenia syndrome (FTLS) in Henan Province, China: discovery of a new bunyavirus. PLoS Pathog. 2011;7:e1002369. 25. Huffman JH, Sidwell RW, Khare GP, et al. In vitro effect of 1-β-D-ribofuranosyl-1,2,4-triazole-3-carboxamide (Virazole, ICN 1229) on deoxyribonucleic acid and ribonucleic acid viruses. Antimicrob Agents Chemother. 1973;3:235-41. 27. Fernandez H, Banks G, Smith R. Ribavirin: a clinical overview. Eur J Epidemiol. 1986;2:1-14. 17. Pancheva S, Dundarova D, Remichkova M. Potentiating effect of mizoribine on the anti-herpes virus activity of acyclovir. Z Naturforsch C. 2002;57:902-4. 22. Canonico PG, Jahrling PB, Pannier WL. Antiviral efficacy of pyrazofurin against selected RNA viruses. Antiviral Res. 1982;2:331-7. 28. Bausch DG, Hadi CM, Khan SH, et al. Review of the literature and proposed guidelines for the use of oral ribavirin as postexposure prophylaxis for Lassa fever. Clin Infect Dis. 2010;51:1435-41. 6. Kim KH, Yi J, Kim G, et al. Severe fever with thrombocytopenia syndrome, South Korea, 2012. Emerg Infect Dis. 2013;19:1892-4. 1. Yu XJ, Liang MF, Zhang SY, et al. Fever with thrombocytopenia associated with a novel bunyavirus in China. N Engl J Med. 2011;364:1523-32. 19. Hosoya M, Shigeta S, Ishii T, et al. Comparative inhibitory effects of various nucleoside and nonnucleoside analogues on replication of influenza virus types A and B in vitro and in ovo. J Infect Dis. 1993;168:641-6. 10. Chen H, Hu K, Zou J, et al. A cluster of cases of human-to-human transmission caused by severe fever with thrombocytopenia syndrome bunyavirus. Int J Infect Dis. 2013;17:e206-8. 29. Liu Y, Wu B, Paessler S, et al. The pathogenesis of SFTSV infection in IFNα/β knockout mice: insights into the pathologic mechanisms of a new viral hemorrhagic fever. J Virol. 2014;88:1781-6. 7. Zhang YZ, Zhou DJ, Qin XC, et al. The ecology, genetic diversity, and phylogeny of Huaiyangshan virus in China. J Virol. 2012;86:2864-8. 21. Reed LJ, Muench H. A simple method of estimating fifty per cent endpoints. Am J Epidemiol. 1938;27:493-7. 4. Liu Y, Li Q, Hu W, et al. Person-to-person transmission of severe fever with thrombocytopenia syndrome virus. Vector Borne Zoonotic Dis. 2012;12:156-60. 15. Graci JD, Cameron CE. Mechanisms of action of ribavirin against distinct viruses. Rev Med Virol. 2006;16:37-48. 12. McCormick JB, King IJ, Webb PA, et al. Lassa fever. Effective therapy with ribavirin. N Engl J Med. 1986;314:20-6. 3. Gai ZT, Zhang Y, Liang MF, et al. Clinical progress and risk factors for death in severe fever with thrombocytopenia syndrome patients. J Infect Dis. 2012;206:1095-102. 20. Saijo M, Morikawa S, Fukushi S, et al. Inhibitory effect of mizoribine and ribavirin on the replication of severe acute respiratory syndrome (SARS)-associated coronavirus. Antiviral Res. 2005;66:159-63. 22 23 24 25 26 27 28 29 30 31 10 32 11 33 12 13 14 15 16 17 18 19 1 2 3 4 5 6 7 8 9 20 21 |
| References_xml | – reference: 11. Tang X, Wu W, Wang H, et al. Human-to-human transmission of severe fever with thrombocytopenia syndrome bunyavirus through contact with infectious blood. J Infect Dis. 2013;207:736-9. – reference: 2. Xu B, Liu L, Huang X, et al. Metagenomic analysis of fever, thrombocytopenia and leukopenia syndrome (FTLS) in Henan Province, China: discovery of a new bunyavirus. PLoS Pathog. 2011;7:e1002369. – reference: 5. Takahashi T, Maeda K, Suzuki T, et al. The first identification and retrospective study of severe fever with thrombocytopenia syndrome in Japan. J Infect Dis. 2014;209:816-27. – reference: 18. Shigeta S. Recent progress in antiviral chemotherapy for respiratory syncytial virus infections. Expert Opin Investig Drugs. 2000;9:221-35. – reference: 30. Sun Y, Jin C, Zhan F, et al. Host cytokine storm is associated with disease severity of severe fever with thrombocytopenia syndrome. J Infect Dis. 2012;206:1085-94. – reference: 6. Kim KH, Yi J, Kim G, et al. Severe fever with thrombocytopenia syndrome, South Korea, 2012. Emerg Infect Dis. 2013;19:1892-4. – reference: 10. Chen H, Hu K, Zou J, et al. A cluster of cases of human-to-human transmission caused by severe fever with thrombocytopenia syndrome bunyavirus. Int J Infect Dis. 2013;17:e206-8. – reference: 22. Canonico PG, Jahrling PB, Pannier WL. Antiviral efficacy of pyrazofurin against selected RNA viruses. Antiviral Res. 1982;2:331-7. – reference: 21. Reed LJ, Muench H. A simple method of estimating fifty per cent endpoints. Am J Epidemiol. 1938;27:493-7. – reference: 20. Saijo M, Morikawa S, Fukushi S, et al. Inhibitory effect of mizoribine and ribavirin on the replication of severe acute respiratory syndrome (SARS)-associated coronavirus. Antiviral Res. 2005;66:159-63. – reference: 13. Lange CM, Jacobson IM, Rice CM, et al. Emerging therapies for the treatment of hepatitis C. EMBO Mol Med. 2014;6:4-15. – reference: 26. Yokota S. Mizoribine: mode of action and effects in clinical use. Pediatr Int. 2002;44:196-8. – reference: 17. Pancheva S, Dundarova D, Remichkova M. Potentiating effect of mizoribine on the anti-herpes virus activity of acyclovir. Z Naturforsch C. 2002;57:902-4. – reference: 15. Graci JD, Cameron CE. Mechanisms of action of ribavirin against distinct viruses. Rev Med Virol. 2006;16:37-48. – reference: 16. Li S, Xue C, Fu Y, et al. Sporadic case infected by severe fever with thrombocytopenia syndrome bunyavirus in a non-epidemic region of China. Biosci Trends. 2011;5:273-6. – reference: 33. Lanford RE, Guerra B, Lee H, et al. Antiviral effect and virus-host interactions in response to alpha interferon, gamma interferon, poly(I)-poly(C), tumor necrosis factor alpha, and ribavirin in hepatitis C virus subgenomic replicons. J Virol. 2003;77:1092-104. – reference: 19. Hosoya M, Shigeta S, Ishii T, et al. Comparative inhibitory effects of various nucleoside and nonnucleoside analogues on replication of influenza virus types A and B in vitro and in ovo. J Infect Dis. 1993;168:641-6. – reference: 27. Fernandez H, Banks G, Smith R. Ribavirin: a clinical overview. Eur J Epidemiol. 1986;2:1-14. – reference: 3. Gai ZT, Zhang Y, Liang MF, et al. Clinical progress and risk factors for death in severe fever with thrombocytopenia syndrome patients. J Infect Dis. 2012;206:1095-102. – reference: 7. Zhang YZ, Zhou DJ, Qin XC, et al. The ecology, genetic diversity, and phylogeny of Huaiyangshan virus in China. J Virol. 2012;86:2864-8. – reference: 12. McCormick JB, King IJ, Webb PA, et al. Lassa fever. Effective therapy with ribavirin. N Engl J Med. 1986;314:20-6. – reference: 32. Liu W, Lu QB, Cui N, et al. Case-fatality ratio and effectiveness of ribavirin therapy among hospitalized patients in China who had severe fever with thrombocytopenia syndrome. Clin Infect Dis. 2013;57:1292-9. – reference: 1. Yu XJ, Liang MF, Zhang SY, et al. Fever with thrombocytopenia associated with a novel bunyavirus in China. N Engl J Med. 2011;364:1523-32. – reference: 24. Reed C, Lin K, Wilhelmsen C, et al. Aerosol exposure to Rift Valley fever virus causes earlier and more severe neuropathology in the murine model, which has important implications for therapeutic development. PLoS Negl Trop Dis. 2013;7:e2156. – reference: 4. Liu Y, Li Q, Hu W, et al. Person-to-person transmission of severe fever with thrombocytopenia syndrome virus. Vector Borne Zoonotic Dis. 2012;12:156-60. – reference: 25. Huffman JH, Sidwell RW, Khare GP, et al. In vitro effect of 1-β-D-ribofuranosyl-1,2,4-triazole-3-carboxamide (Virazole, ICN 1229) on deoxyribonucleic acid and ribonucleic acid viruses. Antimicrob Agents Chemother. 1973;3:235-41. – reference: 28. Bausch DG, Hadi CM, Khan SH, et al. 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| Title | Effects of Ribavirin on Severe Fever with Thrombocytopenia Syndrome Virus In Vitro |
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