1887

Abstract

Avian bornaviruses are the causative agents of proventricular dilatation disease (PDD), a widely distributed and often fatal disease in captive psittacines. Because neither specific prevention measures nor therapies against PDD and bornavirus infections are currently available, new antiviral strategies are required to improve animal health. We show here that the nucleoside analogue ribavirin inhibited bornavirus activity in a polymerase reconstitution assay and reduced viral load in avian cell lines infected with two different parrot bornaviruses. Furthermore, we observed that ribavirin enhanced type I IFN signalling in avian cells. Combined treatment of avian bornavirus-infected cells with ribavirin and recombinant IFN-α strongly enhanced the antiviral efficiency compared to either drug alone. The combined use of ribavirin and type I IFN might represent a promising new strategy for therapeutic treatment of captive parrots persistently infected with avian bornaviruses.

Keyword(s): type I interferon
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2016-09-01
2020-04-02
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References

  1. Afonso C. L., Amarasinghe G. K., Bányai K., Bào Y., Basler C. F., Bavari S., Bejerman N., Blasdell K. R., Briand F. X. et al. 2016; Taxonomy of the order Mononegavirales: update 2016. Arch Virol161:2351–2360 [CrossRef][PubMed]
    [Google Scholar]
  2. Arias A., Arnold J. J., Sierra M., Smidansky E. D., Domingo E., Cameron C. E.. 2008; Determinants of RNA-dependent RNA polymerase (in)fidelity revealed by kinetic analysis of the polymerase encoded by a foot-and-mouth disease virus mutant with reduced sensitivity to ribavirin. J Virol82:12346–12355 [CrossRef][PubMed]
    [Google Scholar]
  3. Day C. W., Smee D. F., Julander J. G., Yamshchikov V. F., Sidwell R. W., Morrey J. D.. 2005; Error-prone replication of West Nile virus caused by ribavirin. Antiviral Res67:38–45 [CrossRef][PubMed]
    [Google Scholar]
  4. Fukuchi Y., Furihata T., Hashizume M., Iikura M., Chiba K.. 2010; Characterization of ribavirin uptake systems in human hepatocytes. J Hepatol52:486–492 [CrossRef][PubMed]
    [Google Scholar]
  5. Graci J. D., Harki D. A., Korneeva V. S., Edathil J. P., Too K., Franco D., Smidansky E. D., Paul A. V., Peterson B. R. et al. 2007; Lethal mutagenesis of poliovirus mediated by a mutagenic pyrimidine analogue. J Virol81:11256–11266 [CrossRef][PubMed]
    [Google Scholar]
  6. Gray P., Hoppes S., Suchodolski P., Mirhosseini N., Payne S., Villanueva I., Shivaprasad H. L., Honkavuori K. S., Briese T. et al. 2010; Use of avian bornavirus isolates to induce proventricular dilatation disease in conures. Emerg Infect Dis16:473–479 [CrossRef][PubMed]
    [Google Scholar]
  7. Gu C. J., Zheng C. Y., Zhang Q., Shi L. L., Li Y., Qu S. F.. 2006; An antiviral mechanism investigated with ribavirin as an RNA virus mutagen for foot-and-mouth disease virus. J Biochem Mol Biol39:9–15[PubMed][CrossRef]
    [Google Scholar]
  8. Heffels-Redmann U., Enderlein D., Herzog S., Herden C., Piepenbring A., Neumann D., Müller H., Capelli S., Müller H. et al. 2011; Occurrence of avian bornavirus infection in captive psittacines in various European countries and its association with proventricular dilatation disease. Avian Pathol40:419–426 [CrossRef][PubMed]
    [Google Scholar]
  9. Hofmann W. P., Herrmann E., Sarrazin C., Zeuzem S.. 2008; Ribavirin mode of action in chronic hepatitis C: from clinical use back to molecular mechanisms. Liver Int28:1332–1343 [CrossRef][PubMed]
    [Google Scholar]
  10. Honkavuori K. S., Shivaprasad H. L., Williams B. L., Quan P. L., Hornig M., Street C., Palacios G., Hutchison S. K., Franca M. et al. 2008; Novel borna virus in psittacine birds with proventricular dilatation disease. Emerg Infect Dis14:1883–1886 [CrossRef][PubMed]
    [Google Scholar]
  11. Hoppes S. M., Tizard I., Shivaprasad H. L.. 2013; Avian bornavirus and proventricular dilatation disease: diagnostics, pathology, prevalence, and control. Vet Clin North Am Exot Anim Pract16:339–355 [CrossRef][PubMed]
    [Google Scholar]
  12. Jordan I., Briese T., Averett D. R., Lipkin W. I.. 1999; Inhibition of borna disease virus replication by ribavirin. J Virol73:7903–7906[PubMed]
    [Google Scholar]
  13. Juozapaitis M., Aguiar Moreira É., Mena I., Giese S., Riegger D., Pohlmann A., Höper D., Zimmer G., Beer M. et al. 2014; An infectious bat-derived chimeric influenza virus harbouring the entry machinery of an influenza A virus. Nat Commun5:44–48 [CrossRef]
    [Google Scholar]
  14. Kojima S., Honda T., Matsumoto Y., Tomonaga K.. 2014; Heat stress is a potent stimulus for enhancing rescue efficiency of recombinant Borna disease virus. Microbiol Immunol58:636–642 [CrossRef][PubMed]
    [Google Scholar]
  15. Kuhn J. H., Dürrwald R., Bào Y., Briese T., Carbone K., Clawson A. N., deRisi J. L., Garten W., Jahrling P. B. et al. 2015; Taxonomic reorganization of the family Bornaviridae . Arch Virol160:621–632 [CrossRef][PubMed]
    [Google Scholar]
  16. Lee B. J., Matsunaga H., Ikuta K., Tomonaga K.. 2008; Ribavirin inhibits Borna disease virus proliferation and fatal neurological diseases in neonatally infected gerbils. Antiviral Res80:380–384 [CrossRef][PubMed]
    [Google Scholar]
  17. Leyssen P., Balzarini J., De Clercq E., Neyts J.. 2005; The predominant mechanism by which ribavirin exerts its antiviral activity in vitro against flaviviruses and paramyxoviruses is mediated by inhibition of IMP dehydrogenase. J Virol79:1943–1947 [CrossRef][PubMed]
    [Google Scholar]
  18. Liu W. L., Yang H. C., Su W. C., Wang C. C., Chen H. L., Wang H. Y., Huang W. H., Chen D. S., Lai M. Y.. 2012; Ribavirin enhances the action of interferon-α against hepatitis C virus by promoting the p53 activity through the ERK1/2 pathway. PLoS One7:e43824 [CrossRef][PubMed]
    [Google Scholar]
  19. Mirhosseini N., Gray P. L., Hoppes S., Tizard I., Shivaprasad H. L., Payne S.. 2011; Proventricular dilatation disease in cockatiels (Nymphicus hollandicus) after infection with a genotype 2 avian bornavirus. J Avian Med Surg25:199–204 [CrossRef][PubMed]
    [Google Scholar]
  20. Mizutani T., Inagaki H., Araki K., Kariwa H., Arikawa J., Takashima I.. 1998; Inhibition of Borna disease virus replication by ribavirin in persistently infected cells. Arch Virol143:2039–2044 [CrossRef][PubMed]
    [Google Scholar]
  21. Mizutani T., Inagaki H., Hayasaka D., Shuto S., Minakawa N., Matsuda A., Kariwa H., Takashima I.. 1999; Transcriptional control of borna disease virus (BDV) in persistently BDV-infected cells. Arch Virol144:1937–1946 [CrossRef][PubMed]
    [Google Scholar]
  22. Moreno H., Gallego I., Sevilla N., de la Torre J. C., Domingo E., Martin V.. 2011; Ribavirin can be mutagenic for arenaviruses. J Virol85:7246–7255 [CrossRef][PubMed]
    [Google Scholar]
  23. Mori K., Ikeda M., Ariumi Y., Dansako H., Wakita T., Kato N.. 2011; Mechanism of action of ribavirin in a novel hepatitis C virus replication cell system. Virus Res157:61–70 [CrossRef][PubMed]
    [Google Scholar]
  24. Musser J. M., Heatley J. J., Koinis A. V., Suchodolski P. F., Guo J., Escandon P., Tizard I. R.. 2015; Ribavirin inhibits parrot bornavirus 4 replication in cell culture. PLoS One10:e0134080 [CrossRef][PubMed]
    [Google Scholar]
  25. Ölschläger S., Neyts J., Günther S.. 2011; Depletion of GTP pool is not the predominant mechanism by which ribavirin exerts its antiviral effect on Lassa virus. Antiviral Res91:89–93 [CrossRef][PubMed]
    [Google Scholar]
  26. Parker W. B.. 2005; Metabolism and antiviral activity of ribavirin. Virus Res107:165–171 [CrossRef][PubMed]
    [Google Scholar]
  27. Pauly M. D., Lauring A. S.. 2015; Effective lethal mutagenesis of influenza virus by three nucleoside analogs. J Virol89:3584–3597 [CrossRef][PubMed]
    [Google Scholar]
  28. Penski N., Härtle S., Rubbenstroth D., Krohmann C., Ruggli N., Schusser B., Pfann M., Reuter A., Gohrbandt S. et al. 2011; Highly pathogenic avian influenza viruses do not inhibit interferon synthesis in infected chickens but can override the interferon-induced antiviral state. J Virol85:7730–7741 [CrossRef][PubMed]
    [Google Scholar]
  29. Pfeiffer J. K., Kirkegaard K.. 2005; Ribavirin resistance in hepatitis C virus replicon-containing cell lines conferred by changes in the cell line or mutations in the replicon RNA. J Virol79:2346–2355 [CrossRef][PubMed]
    [Google Scholar]
  30. Philadelpho N. A., Rubbenstroth D., Guimarães M. B., Piantino Ferreira A. J.. 2014; Survey of bornaviruses in pet psittacines in Brazil reveals a novel parrot bornavirus. Vet Microbiol174:584–590 [CrossRef][PubMed]
    [Google Scholar]
  31. Piepenbring A. K., Enderlein D., Herzog S., Kaleta E. F., Heffels-Redmann U., Ressmeyer S., Herden C., Lierz M.. 2012; Pathogenesis of avian bornavirus in experimentally infected cockatiels. Emerg Infect Dis18:234–241 [CrossRef][PubMed]
    [Google Scholar]
  32. Reuter A., Ackermann A., Kothlow S., Rinder M., Kaspers B., Staeheli P.. 2010; Avian bornaviruses escape recognition by the innate immune system. Viruses2:927–938 [CrossRef][PubMed]
    [Google Scholar]
  33. Rinder M., Ackermann A., Kempf H., Kaspers B., Korbel R., Staeheli P.. 2009; Broad tissue and cell tropism of avian bornavirus in parrots with proventricular dilatation disease. J Virol83:5401–5407 [CrossRef][PubMed]
    [Google Scholar]
  34. Rubbenstroth D., Rinder M., Kaspers B., Staeheli P.. 2012; Efficient isolation of avian bornaviruses (ABV) from naturally infected psittacine birds and identification of a new ABV genotype from a salmon-crested cockatoo (Cacatua moluccensis). Vet Microbiol161:36–42 [CrossRef][PubMed]
    [Google Scholar]
  35. Rubbenstroth D., Brosinski K., Rinder M., Olbert M., Kaspers B., Korbel R., Staeheli P.. 2014; No contact transmission of avian bornavirus in experimentally infected cockatiels (Nymphicus hollandicus) and domestic canaries (Serinus canaria forma domestica). Vet Microbiol172:146–156 [CrossRef][PubMed]
    [Google Scholar]
  36. Schultz U., Rinderle C., Sekellick M. J., Marcus P. I., Staeheli P.. 1995; Recombinant chicken interferon from Escherichia coli and transfected COS cells is biologically active. Eur J Biochem229:73–76 [CrossRef][PubMed]
    [Google Scholar]
  37. Severson W. E., Schmaljohn C. S., Javadian A., Jonsson C. B.. 2003; Ribavirin causes error catastrophe during Hantaan virus replication. J Virol77:481–488 [CrossRef][PubMed]
    [Google Scholar]
  38. Staeheli P., Rinder M., Kaspers B.. 2010; Avian bornavirus associated with fatal disease in psittacine birds. J Virol84:6269–6275 [CrossRef][PubMed]
    [Google Scholar]
  39. Stevenson N. J., Murphy A. G., Bourke N. M., Keogh C. A., Hegarty J. E., O'Farrelly C.. 2011; Ribavirin enhances IFN-α signalling and MxA expression: a novel immune modulation mechanism during treatment of HCV. PLoS One6:e27866 [CrossRef][PubMed]
    [Google Scholar]
  40. Su W. C., Liu W. L., Cheng C. W., Chou Y. B., Hung K. H., Huang W. H., Wu C. L., Li Y. T., Shiau A. L., Lai M. Y.. 2009; Ribavirin enhances interferon signaling via stimulation of mTOR and p53 activities. FEBS Lett583:2793–2798 [CrossRef][PubMed]
    [Google Scholar]
  41. Te H. S., Randall G., Jensen D. M.. 2007; Mechanism of action of ribavirin in the treatment of chronic hepatitis C. Gastroenterol Hepatol3:218–225
    [Google Scholar]
  42. Thomas E., Feld J. J., Li Q., Hu Z., Fried M. W., Liang T. J.. 2011; Ribavirin potentiates interferon action by augmenting interferon-stimulated gene induction in hepatitis C virus cell culture models. Hepatology53:32–41 [CrossRef][PubMed]
    [Google Scholar]
  43. Yanai H., Hayashi Y., Watanabe Y., Ohtaki N., Kobayashi T., Nozaki Y., Ikuta K., Tomonaga K.. 2006; Development of a novel borna disease virus reverse genetics system using RNA polymerase II promoter and SV40 nuclear import signal. Microbes Infect8:1522–1529 [CrossRef][PubMed]
    [Google Scholar]
  44. Young K. C., Lindsay K. L., Lee K. J., Liu W. C., He J. W., Milstein S. L., Lai M. M. C.. 2003; Identification of a ribavirin-resistant NS5B mutation of hepatitis C virus during ribavirin monotherapy. Hepatology38:869–878 [CrossRef][PubMed]
    [Google Scholar]
  45. Zimmermann V., Rinder M., Kaspers B., Staeheli P., Rubbenstroth D.. 2014; Impact of antigenic diversity on laboratory diagnosis of avian bornavirus infections in birds. J Vet Diagn Invest26:769–777 [CrossRef][PubMed]
    [Google Scholar]
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