1887

Abstract

Hendra virus (HeV) and Nipah virus (NiV) are recently emerged, closely related and highly pathogenic paramyxoviruses that cause severe disease such as encephalitis in animals and humans with fatality rates of up to 75 %. Due to their high case fatality rate following human infection and because of the lack of effective vaccines or therapy, they are classified as Biosafety Level 4 pathogens. A recent study reported that chloroquine, an anti-malarial drug, was effective in preventing NiV and HeV infection in cell culture experiments. In the present study, the antiviral efficacy of chloroquine was analysed, individually and in combination with ribavirin, in the treatment of NiV and HeV infection in experiments, using a golden hamster model. Although the results confirmed the strong antiviral activity of both drugs in inhibiting viral spread , they did not prove to be protective in the model. Ribavirin delayed death from viral disease in NiV-infected hamsters by approximately 5 days, but no significant effect in HeV-infected hamsters was observed. Chloroquine did not protect hamsters when administered either individually or in combination with ribavirin, the latter indicating the lack of a favourable drug–drug interaction.

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2010-03-01
2019-11-17
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References

  1. Aljofan, M., Porotto, M., Moscona, A. & Mungall, B. A. ( 2008; ). Development and validation of a chemiluminescent immunodetection assay amenable to high throughput screening of antiviral drugs for Nipah and Hendra virus. J Virol Methods 149, 12–19.[CrossRef]
    [Google Scholar]
  2. Aljofan, M., Saubern, S., Meyer, A. G., Marsh, G., Meers, J. & Mungall, B. A. ( 2009; ). Characteristics of Nipah virus and Hendra virus replication in different cell lines and their suitability for antiviral screening. Virus Res 142, 92–99.[CrossRef]
    [Google Scholar]
  3. CDC ( 1999; ). Update: outbreak of Nipah virus – Malaysia and Singapore, 1999. MMWR Morb Mortal Wkly Rep 48, 335–337.
    [Google Scholar]
  4. Chadha, M. S., Comer, J. A., Lowe, L., Rota, P. A., Rollin, P. E., Bellini, W. J., Ksiazek, T. G. & Mishra, A. ( 2006; ). Nipah virus-associated encephalitis outbreak, Siliguri, India. Emerg Infect Dis 12, 235–240.[CrossRef]
    [Google Scholar]
  5. Chong, H. T., Kamarulzaman, A., Tan, C. T., Goh, K. J., Thayaparan, T., Kunjapan, S. R., Chew, N. K., Chua, K. B. & Lam, S. K. ( 2001; ). Treatment of acute Nipah encephalitis with ribavirin. Ann Neurol 49, 810–813.[CrossRef]
    [Google Scholar]
  6. Chua, K. B., Goh, K. J., Wong, K. T., Kamarulzaman, A., Tan, P. S., Ksiazek, T. G., Zaki, S. R., Paul, G., Lam, S. K. & Tan, C. T. ( 1999; ). Fatal encephalitis due to Nipah virus among pig-farmers in Malaysia. Lancet 354, 1257–1259.[CrossRef]
    [Google Scholar]
  7. Chua, K. B., Bellini, W. J., Rota, P. A., Harcourt, B. H., Tamin, A., Lam, S. K., Ksiazek, T. G., Rollin, P. E., Zaki, S. R. & other authors ( 2000a; ). Nipah virus: a recently emergent deadly paramyxovirus. Science 288, 1432–1435.[CrossRef]
    [Google Scholar]
  8. Chua, K. B., Lam, S. K., Tan, C. T., Hooi, P. S., Goh, K. J., Chew, N. K., Tan, K. S., Kamarulzaman, A. & Wong, K. T. ( 2000b; ). High mortality in Nipah encephalitis is associated with presence of virus in cerebrospinal fluid. Ann Neurol 48, 802–805.[CrossRef]
    [Google Scholar]
  9. Chua, K. B., Koh, C. L., Hooi, P. S., Wee, K. F., Khong, J. H., Chua, B. H., Chan, Y. P., Lim, M. E. & Lam, S. K. ( 2002; ). Isolation of Nipah virus from Malaysian Island flying-foxes. Microbes Infect 4, 145–151.[CrossRef]
    [Google Scholar]
  10. Crotty, S., Cameron, C. & Andino, R. ( 2002; ). Ribavirin's antiviral mechanism of action: lethal mutagenesis? J Mol Med 80, 86–95.[CrossRef]
    [Google Scholar]
  11. Diederich, S., Thiel, L. & Maisner, A. ( 2008; ). Role of endocytosis and cathepsin-mediated activation in Nipah virus entry. Virology 375, 391–400.[CrossRef]
    [Google Scholar]
  12. Drexler, J. F., Corman, V. M., Gloza-Rausch, F., Seebens, A., Annan, A., Ipsen, A., Kruppa, T., Muller, M. A., Kalko, E. K. & other authors ( 2009; ). Henipavirus RNA in African bats. PLoS One 4, e6367 [CrossRef]
    [Google Scholar]
  13. Georges-Courbot, M. C., Contamin, H., Faure, C., Loth, P., Baize, S., Leyssen, P., Neyts, J. & Deubel, V. ( 2006; ). Poly(I)-poly(C12U) but not ribavirin prevents death in a hamster model of Nipah virus infection. Antimicrob Agents Chemother 50, 1768–1772.[CrossRef]
    [Google Scholar]
  14. Guillaume, V., Wong, K. T., Looi, R. Y., Georges-Courbot, M. C., Barrot, L., Buckland, R., Wild, T. F. & Horvat, B. ( 2009; ). Acute Hendra virus infection: analysis of the pathogenesis and passive antibody protection in the hamster model. Virology 387, 459–465.[CrossRef]
    [Google Scholar]
  15. Gurley, E. S., Montgomery, J. M., Hossain, M. J., Bell, M., Azad, A. K., Islam, M. R., Molla, M. A., Carroll, D. S., Ksiazek, T. G. & other authors ( 2007; ). Person-to-person transmission of Nipah virus in a Bangladeshi community. Emerg Infect Dis 13, 1031–1037.[CrossRef]
    [Google Scholar]
  16. Halpin, K., Young, P. L., Field, H. & Mackenzie, J. S. ( 1999; ). Newly discovered viruses of flying foxes. Vet Microbiol 68, 83–87.[CrossRef]
    [Google Scholar]
  17. Halpin, K., Young, P. L., Field, H. E. & Mackenzie, J. S. ( 2000; ). Isolation of Hendra virus from pteropid bats: a natural reservoir of Hendra virus. J Gen Virol 81, 1927–1932.
    [Google Scholar]
  18. Hanna, J. N., McBride, W. J., Brookes, D. L., Shield, J., Taylor, C. T., Smith, I. L., Craig, S. B. & Smith, G. A. ( 2006; ). Hendra virus infection in a veterinarian. Med J Aust 185, 562–564.
    [Google Scholar]
  19. Harcourt, B. H., Tamin, A., Ksiazek, T. G., Rollin, P. E., Anderson, L. J., Bellini, W. J. & Rota, P. A. ( 2000; ). Molecular characterization of Nipah virus, a newly emergent paramyxovirus. Virology 271, 334–349.[CrossRef]
    [Google Scholar]
  20. Harcourt, B. H., Lowe, L., Tamin, A., Liu, X., Bankamp, B., Bowden, N., Rollin, P. E., Comer, J. A., Ksiazek, T. G. & other authors ( 2005; ). Genetic characterization of Nipah virus, Bangladesh, 2004. Emerg Infect Dis 11, 1594–1597.[CrossRef]
    [Google Scholar]
  21. Honda, Y., Hosoya, M., Ishii, T., Shigeta, S. & Suzuki, H. ( 1994; ). Effect of ribavirin on subacute sclerosing panencephalitis virus infections in hamsters. Antimicrob Agents Chemother 38, 653–655.[CrossRef]
    [Google Scholar]
  22. Hossain, M. J., Gurley, E. S., Montgomery, J. M., Bell, M., Carroll, D. S., Hsu, V. P., Formenty, P., Croisier, A., Bertherat, E. & other authors ( 2008; ). Clinical presentation of Nipah virus infection in Bangladesh. Clin Infect Dis 46, 977–984.[CrossRef]
    [Google Scholar]
  23. Hsu, V. P., Hossain, M. J., Parashar, U. D., Ali, M. M., Ksiazek, T. G., Kuzmin, I., Niezgoda, M., Rupprecht, C., Bresee, J. & Breiman, R. F. ( 2004; ). Nipah virus encephalitis reemergence, Bangladesh. Emerg Infect Dis 10, 2082–2087.[CrossRef]
    [Google Scholar]
  24. Ishii, T., Hosoya, M., Mori, S., Shigeta, S. & Suzuki, H. ( 1996; ). Effective ribavirin concentration in hamster brains for antiviral chemotherapy for subacute sclerosing panencephalitis. Antimicrob Agents Chemother 40, 241–243.
    [Google Scholar]
  25. Lee, B. ( 2007; ). Envelope–receptor interactions in Nipah virus pathobiology. Ann N Y Acad Sci 1102, 51–65.[CrossRef]
    [Google Scholar]
  26. Luby, S. P., Rahman, M., Hossain, M. J., Blum, L. S., Husain, M. M., Gurley, E., Khan, R., Ahmed, B. N., Rahman, S. & other authors ( 2006; ). Foodborne transmission of Nipah virus, Bangladesh. Emerg Infect Dis 12, 1888–1894.[CrossRef]
    [Google Scholar]
  27. Mohd Nor, M. N., Gan, C. H. & Ong, B. L. ( 2000; ). Nipah virus infection of pigs in peninsular Malaysia. Rev Sci Tech 19, 160–165.
    [Google Scholar]
  28. Murray, K., Rogers, R., Selvey, L., Selleck, P., Hyatt, A., Gould, A., Gleeson, L., Hooper, P. & Westbury, H. ( 1995a; ). A novel morbillivirus pneumonia of horses and its transmission to humans. Emerg Infect Dis 1, 31–33.[CrossRef]
    [Google Scholar]
  29. Murray, K., Selleck, P., Hooper, P., Hyatt, A., Gould, A., Gleeson, L., Westbury, H., Hiley, L., Selvey, L. & other authors ( 1995b; ). A morbillivirus that caused fatal disease in horses and humans. Science 268, 94–97.[CrossRef]
    [Google Scholar]
  30. O'Sullivan, J. D., Allworth, A. M., Paterson, D. L., Snow, T. M., Boots, R., Gleeson, L. J., Gould, A. R., Hyatt, A. D. & Bradfield, J. ( 1997; ). Fatal encephalitis due to novel paramyxovirus transmitted from horses. Lancet 349, 93–95.[CrossRef]
    [Google Scholar]
  31. Pallister, J., Middleton, D., Crameri, G., Yamada, M., Klein, R., Hancock, T. J., Foord, A., Shiell, B., Michalski, W. & other authors ( 2009; ). Chloroquine administration does not prevent Nipah virus infection and disease in ferrets. J Virol 83, 11979–11982.[CrossRef]
    [Google Scholar]
  32. Paterson, D. L., Murray, P. K. & McCormack, J. G. ( 1998; ). Zoonotic disease in Australia caused by a novel member of the Paramyxoviridae. Clin Infect Dis 27, 112–118.[CrossRef]
    [Google Scholar]
  33. Porotto, M., Orefice, G., Yokoyama, C. C., Mungall, B. A., Realubit, R., Sganga, M. L., Aljofan, M., Whitt, M., Glickman, F. & Moscona, A. ( 2009; ). Simulating henipavirus multicycle replication in a screening assay leads to identification of a promising candidate for therapy. J Virol 83, 5148–5155.[CrossRef]
    [Google Scholar]
  34. ProMED-mail ( 2008a; ). Hendra virus, human, equine – Australia (07): Queensland. ProMED-mail 2008, 21 Aug 20080821.2606.
  35. ProMED-mail ( 2008b; ). Nipah virus – Bangladesh (04): transmission. ProMED-mail 2008, 06 Apr 20080406.1263.
  36. ProMED-mail ( 2009a; ). Hendra virus, human, equine – Australia (02): Queensland. ProMED-mail 2009, 26 Aug 20090826.2998.
  37. ProMED-mail ( 2009b; ). Hendra virus, human, equine – Australia (04): Queensland fatal. ProMED-mail 2009, 03 Sep 20090903.3098.
  38. ProMED-mail ( 2009c; ). Hendra virus, human, equine – Australia (05): Queensland. ProMED-mail 2009, 10 Sep 20090910.3198.
  39. Reed, L. J. & Muench, H. ( 1938; ). A simple method of estimating fifty per cent endpoint. Am J Hyg 27, 493–497.
    [Google Scholar]
  40. Reynes, J. M., Counor, D., Ong, S., Faure, C., Seng, V., Molia, S., Walston, J., Georges-Courbot, M. C., Deubel, V. & Sarthou, J. L. ( 2005; ). Nipah virus in Lyle's flying foxes, Cambodia. Emerg Infect Dis 11, 1042–1047.[CrossRef]
    [Google Scholar]
  41. Sejvar, J. J., Hossain, J., Saha, S. K., Gurley, E. S., Banu, S., Hamadani, J. D., Faiz, M. A., Siddiqui, F. M., Mohammad, Q. D. & other authors ( 2007; ). Long-term neurological and functional outcome in Nipah virus infection. Ann Neurol 62, 235–242.[CrossRef]
    [Google Scholar]
  42. Selvey, L. A., Wells, R. M., McCormack, J. G., Ansford, A. J., Murray, K., Rogers, R. J., Lavercombe, P. S., Selleck, P. & Sheridan, J. W. ( 1995; ). Infection of humans and horses by a newly described morbillivirus. Med J Aust 162, 642–645.
    [Google Scholar]
  43. Tan, C. T., Goh, K. J., Wong, K. T., Sarji, S. A., Chua, K. B., Chew, N. K., Murugasu, P., Loh, Y. L., Chong, H. T. & other authors ( 2002; ). Relapsed and late-onset Nipah encephalitis. Ann Neurol 51, 703–708.[CrossRef]
    [Google Scholar]
  44. Wang, L. F., Yu, M., Hansson, E., Pritchard, L. I., Shiell, B., Michalski, W. P. & Eaton, B. T. ( 2000; ). The exceptionally large genome of Hendra virus: support for creation of a new genus within the family Paramyxoviridae. J Virol 74, 9972–9979.[CrossRef]
    [Google Scholar]
  45. Wong, S. C., Ooi, M. H., Wong, M. N., Tio, P. H., Solomon, T. & Cardosa, M. J. ( 2001; ). Late presentation of Nipah virus encephalitis and kinetics of the humoral immune response. J Neurol Neurosurg Psychiatry 71, 552–554.[CrossRef]
    [Google Scholar]
  46. World Health Organization ( 2004; ). Nipah virus outbreak(s) in Bangladesh, January–April 2004. Wkly Epidemiol Rec 79, 168–171.
    [Google Scholar]
  47. Wright, P. J., Crameri, G. & Eaton, B. T. ( 2005; ). RNA synthesis during infection by Hendra virus: an examination by quantitative real-time PCR of RNA accumulation, the effect of ribavirin and the attenuation of transcription. Arch Virol 150, 521–532.[CrossRef]
    [Google Scholar]
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