1887

Abstract

Multiple monkeypox virus (MPXV) animal models have been discussed in previous studies, but no small animal models, nor most non-human primate models, demonstrated the protracted asymptomatic incubation phase seen in systemic human orthopoxvirus illness. Herein, we characterize a black-tailed prairie dog (PD) () model of infection, via intranasal and intradermal exposures, with the two MPXV clades. Daily observations of the animals were made (food consumption, general symptoms, disease presentation), while weights and virus evaluations (ocular, nasal, oropharyngeal, faeces, blood) were obtained/made every third day. Generalized rash became apparent 9–12 days post-infection for all animals. Individual animals demonstrated a range of symptoms consistent with human monkeypox disease. Measurable viraemias and excretas were similar for both clade-representative strains and persisted until at least day 21. Greater morbidity was observed in Congo Basin strain-challenged animals and mortality was observed only in the Congo Basin strain-challenged animals. The PD model is valuable for the study of strain-dependent differences in MPXV. Additionally, the model closely mimics human systemic orthopoxvirus disease and may serve as a valuable non-human surrogate for investigations of antivirals and next generation orthopoxvirus vaccines.

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2009-02-01
2019-11-19
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References

  1. Arita, I. & Gromyko, A. ( 1982; ). Surveillance of orthopoxvirus infections, and associated research, in the period after smallpox eradication. Bull World Health Organ 60, 367–375.
    [Google Scholar]
  2. Arita, I., Jezek, Z., Khodakevich, L. & Ruti, K. ( 1985; ). Human monkeypox: a newly emerged orthopoxvirus zoonosis in the tropical rain forests of Africa. Am J Trop Med Hyg 34, 781–789.
    [Google Scholar]
  3. Boumandouki, P., Bileckot, R., Ibara, J. R., Satounkazi, C., Wassa, W. D., Libama, E., Moudzeo, H., Bolanda, J. D. & Ngokaba, C. ( 2007; ). Simian smallpox (or monkey smallpox): study of 8 cases observed at Impfondo Hospital in Republic of Congo. Bull Soc Pathol Exot 100, 17–21.
    [Google Scholar]
  4. Breman, J. G. & Henderson, D. A. ( 2002; ). Diagnosis and management of smallpox. N Engl J Med 346, 1300–1308.[CrossRef]
    [Google Scholar]
  5. Breman, J. G., Kalisa, R., Steniowski, M. V., Zanotto, E., Gromyko, A. I. & Arita, I. ( 1980; ). Human monkeypox, 1970–79. Bull World Health Organ 58, 165–182.
    [Google Scholar]
  6. Chen, N., Li, G., Liszewski, M. K., Atkinson, J. P., Jahrling, P. B., Feng, Z., Schriewer, J., Buck, C., Wang, C. & other authors ( 2005; ). Virulence differences between monkeypox virus isolates from West Africa and the Congo basin. Virology 340, 46–63.[CrossRef]
    [Google Scholar]
  7. Fenner, F. ( 1948; ). The pathogenesis of the acute exanthems. Lancet 2, 915–920.
    [Google Scholar]
  8. Fenner, F. ( 1990; ). Poxviruses. In Fields Virology, 2nd edn, pp. 2113–2133. Edited by B. N. Fields & D. M. Knipe. New York: Raven Press.
  9. Fine, P. E., Jezek, Z., Grab, B. & Dixon, H. ( 1988; ). The transmission potential of monkeypox virus in human populations. Int J Epidemiol 17, 643–650.[CrossRef]
    [Google Scholar]
  10. Foster, S. O., Brink, E. W., Hutchins, D. L., Pifer, J. M., Lourie, B., Moser, C. R., Cummings, E. C., Kuteyi, O. E., Eke, R. E. & other authors ( 1972; ). Human monkeypox. Bull World Health Organ 46, 569–576.
    [Google Scholar]
  11. Guarner, J., Johnson, B. J., Paddock, C. D., Shieh, W. J., Goldsmith, C. S., Reynolds, M. G., Damon, I. K., Regnery, R. L. & Zaki, S. R. ( 2004; ). Monkeypox transmission and pathogenesis in prairie dogs. Emerg Infect Dis 10, 426–431.[CrossRef]
    [Google Scholar]
  12. Huhn, G. D., Chase, R. A. & Dworkin, M. S. ( 2004; ). Monkeypox in the Western hemisphere. N Engl J Med 350, 1790–1791.[CrossRef]
    [Google Scholar]
  13. Huhn, G. D., Bauer, A. M., Yorita, K., Graham, M. B., Sejvar, J., Likos, A., Damon, I. K., Reynolds, M. G. & Kuehnert, M. J. ( 2005; ). Clinical characteristics of human monkeypox, and risk factors for severe disease. Clin Infect Dis 41, 1742–1751.[CrossRef]
    [Google Scholar]
  14. Hutin, Y. J., Williams, R. J., Malfait, P., Pebody, R., Loparev, V. N., Ropp, S. L., Rodriguez, M., Knight, J. C., Tshioko, F. K. & other authors ( 2001; ). Outbreak of human monkeypox, Democratic Republic of Congo, 1996 to 1997. Emerg Infect Dis 7, 434–438.[CrossRef]
    [Google Scholar]
  15. Hutson, C. L., Lee, K. N., Abel, J., Carroll, D. S., Montgomery, J. M., Olson, V. A., Li, Y., Davidson, W., Hughes, C. & other authors ( 2007; ). Monkeypox zoonotic associations: insights from laboratory evaluation of animals associated with the multi-state US outbreak. Am J Trop Med Hyg 76, 757–768.
    [Google Scholar]
  16. Jezek, Z., Szczeniowski, M., Paluku, K. M. & Mutombo, M. ( 1987; ). Human monkeypox: clinical features of 282 patients. J Infect Dis 156, 293–298.[CrossRef]
    [Google Scholar]
  17. Learned, L. A., Reynolds, M. G., Wassa, D. W., Li, Y., Olson, V. A., Karem, K., Stempora, L. L., Braden, Z. H., Kline, R. & other authors ( 2005; ). Extended interhuman transmission of monkeypox in a hospital community in the Republic of the Congo, 2003. Am J Trop Med Hyg 73, 428–434.
    [Google Scholar]
  18. Lehmann, E. L. ( 1975; ). Nonparametrics: Statistical Methods Based on Ranks. San Francisco: Holden-Day.
  19. Li, Y., Olson, V. A., Laue, T., Laker, M. T. & Damon, I. K. ( 2006; ). Detection of monkeypox virus with real-time PCR assays. J Clin Virol 36, 194–203.[CrossRef]
    [Google Scholar]
  20. Likos, A. M., Sammons, S. A., Olson, V. A., Frace, A. M., Li, Y., Olsen-Rasmussen, M., Davidson, W., Galloway, R., Khristova, M. L. & other authors ( 2005; ). A tale of two clades: monkeypox viruses. J Gen Virol 86, 2661–2672.[CrossRef]
    [Google Scholar]
  21. Marennikova, S. S. & Seluhina, E. M. ( 1976; ). Susceptibility of some rodent species to monkeypox virus, and course of the infection. Bull World Health Organ 53, 13–20.
    [Google Scholar]
  22. Meyer, H., Perrichot, M., Stemmler, M., Emmerich, P., Schmitz, H., Varaine, F., Shungu, R., Tshioko, F. & Formenty, P. ( 2002; ). Outbreaks of disease suspected of being due to human monkeypox virus infection in the Democratic Republic of Congo in 2001. J Clin Microbiol 40, 2919–2921.[CrossRef]
    [Google Scholar]
  23. Mukinda, V. B., Mwema, G., Kilundu, M., Heymann, D. L., Khan, A. S. & Esposito, J. J. ( 1997; ). Re-emergence of human monkeypox in Zaire in 1996. Monkeypox epidemiologic working group. Lancet 349, 1449–1450.[CrossRef]
    [Google Scholar]
  24. Mwanbal, P. T., Tshioko, K. F., Moudi, A., Mukinda, V., Mwema, G. N., Messinger, D., Okito, L., Barakymfyte, D., Malfait, P. & other authors ( 1997; ). Human monkeypox in Kasai Oriental, Zaire (1996–1997). Euro Surveill 2, 33–35.
    [Google Scholar]
  25. Reed, K. D., Melski, J. W., Graham, M. B., Regnery, R. L., Sotir, M. J., Wegner, M. V., Kazmierczak, J. J., Stratman, E. J., Li, Y. & other authors ( 2004; ). The detection of monkeypox in humans in the Western Hemisphere. N Engl J Med 350, 342–350.[CrossRef]
    [Google Scholar]
  26. Reynolds, M. G., Cono, J., Curns, A., Holman, R. C., Likos, A., Regnery, R., Treadwell, T. & Damon, I. ( 2004; ). Human monkeypox. Lancet Infect Dis 4, 604–605.[CrossRef]
    [Google Scholar]
  27. Reynolds, M. G., Yorita, K. L., Kuehnert, M. J., Davidson, W. B., Huhn, G. D., Holman, R. C. & Damon, I. K. ( 2006; ). Clinical manifestations of human monkeypox influenced by route of infection. J Infect Dis 194, 773–780.[CrossRef]
    [Google Scholar]
  28. Rimoin, A. W., Kisalu, N., Kebela-Ilunga, B., Mukaba, T., Wright, L. L., Formenty, P., Wolfe, N. D., Shongo, R. L., Tshioko, F. & other authors ( 2007; ). Endemic human monkeypox, Democratic Republic of Congo, 2001–2004. Emerg Infect Dis 13, 934–937.[CrossRef]
    [Google Scholar]
  29. Shchelukhina, E. M. & Marennikova, S. S. ( 1975; ). Generalized monkeypox in orally infected rabbits and white mice. Vopr Virusol 6, 703–705 (in Russian).
    [Google Scholar]
  30. Tesh, R. B., Watts, D. M., Sbrana, E., Siirin, M., Popov, V. L. & Xiao, S. Y. ( 2004; ). Experimental infection of ground squirrels (Spermophilus tridecemlineatus) with monkeypox virus. Emerg Infect Dis 10, 1563–1567.[CrossRef]
    [Google Scholar]
  31. Xiao, S. Y., Sbrana, E., Watts, D. M., Siirin, M., da Rosa, A. P. & Tesh, R. B. ( 2005; ). Experimental infection of prairie dogs with monkeypox virus. Emerg Infect Dis 11, 539–545.[CrossRef]
    [Google Scholar]
  32. Zaucha, G. M., Jahrling, P. B., Geisbert, T. W., Swearengen, J. R. & Hensley, L. ( 2001; ). The pathology of experimental aerosolized monkeypox virus infection in cynomolgus monkeys (Macaca fascicularis). Lab Invest 81, 1581–1600.[CrossRef]
    [Google Scholar]
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vol. , part 2, pp. 323–333

West African MPXV-challenged prairie dogs (ID-SC route).

Congo Basin MPXV-challenged prairie dogs (ID-SC route).

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