1887

Abstract

We previously demonstrated that small-particle (0.5–3.0 µm) aerosol infection of rhesus monkeys () with cowpox virus (CPXV)-Brighton Red (BR) results in fulminant respiratory tract disease characterized by severe lung parenchymal pathology but only limited systemic virus dissemination and limited classic epidermal pox-like lesion development ( ). Based on these results, and to further develop CPXV as an improved model of human smallpox, we evaluated a novel large-particle aerosol (7.0–9.0 µm) exposure of rhesus monkeys to CPXV-BR and monitored for respiratory tract disease by serial computed tomography (CT). As expected, the upper respiratory tract and large airways were the major sites of virus-induced pathology following large-particle aerosol exposure. Large-particle aerosol CPXV exposure of rhesus macaques resulted in severe upper airway and large airway pathology with limited systemic dissemination.

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2016-08-01
2020-04-05
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References

  1. Aebersold P.. 2012; FDA experience with medical countermeasures under the Animal Rule. Adv Prev Med2012:507571 [CrossRef][PubMed]
    [Google Scholar]
  2. Americo J. L., Moss B., Earl P. L.. 2010; Identification of wild-derived inbred mouse strains highly susceptible to monkeypox virus infection for use as small animal models. J Virol84:8172–8180 [CrossRef][PubMed]
    [Google Scholar]
  3. Bai H., Buller R. M., Chen N., Green M., Nuara A. A.. 2005; Biosynthesis of the IFN-gamma binding protein of ectromelia virus, the causative agent of mousepox. Virology334:41–50 [CrossRef][PubMed]
    [Google Scholar]
  4. Barnewall R. E., Fisher D. A., Robertson A. B., Vales P. A., Knostman K. A., Bigger J. E.. 2012; Inhalational monkeypox virus infection in cynomolgus macaques. Front Cell Infect Microbiol2:117 [CrossRef][PubMed]
    [Google Scholar]
  5. Bohannon J. K., Lackemeyer M. G., Kuhn J. H., Wada J., Bollinger L., Jahrling P. B., Johnson R. F.. 2015; Generation and characterization of large-particle aerosols using a center flow tangential aerosol generator with a non-human-primate, head-only aerosol chamber. Inhal Toxicol27:247–253 [CrossRef][PubMed]
    [Google Scholar]
  6. Born T. L., Morrison L. A., Esteban D. J., VandenBos T., Thebeau L. G., Chen N., Spriggs M. K., Sims J. E., Buller R. M.. 2000; A poxvirus protein that binds to and inactivates IL-18, and inhibits NK cell response. J Immunol164:3246–3254 [CrossRef][PubMed]
    [Google Scholar]
  7. Bray M., Buller M.. 2004; Looking back at smallpox. Clin Infect Dis38:882–889 [CrossRef][PubMed]
    [Google Scholar]
  8. Damon I. K., Damaso C. R., McFadden G.. 2014; Are we there yet? The smallpox research agenda using variola virus. PLoS Pathog10:e1004108 [CrossRef][PubMed]
    [Google Scholar]
  9. Dixon C. W.. 1962; Smallpox London: Churchill;
    [Google Scholar]
  10. Downie A. W., Fedson D. S., Saint Vincent L., Rao A. R., Kempe C. H.. 1969; Haemorrhagic smallpox. J Hyg67:619–629 [CrossRef][PubMed]
    [Google Scholar]
  11. Earl P. L., Americo J. L., Moss B.. 2012; Lethal monkeypox virus infection of CAST/EiJ mice is associated with a deficient gamma interferon response. J Virol86:9105–9112 [CrossRef][PubMed]
    [Google Scholar]
  12. Fenner F.. 1980; Smallpox and its eradication. Aust Nz J Med10:459
    [Google Scholar]
  13. Fenner F.. 1988; The clinical features of smallpox. In Smallpox and Its Eradication Edited by Fenner F., Henderson D. A., Arita I., Jezek Z., Ladnyi I. D.. Geneva, Switzerland: World Health Organization;
    [Google Scholar]
  14. Fenner F., Henderson D. A., Arita I., Jezek J., Ladnyi I. D.. 1988; Smallpox and Its Eradication Geneva, Switzerland: World Health Organization;
    [Google Scholar]
  15. Goff A. J., Chapman J., Foster C., Wlazlowski C., Shamblin J., Lin K., Kreiselmeier N., Mucker E., Paragas J. et al. 2011; A novel respiratory model of infection with monkeypox virus in cynomolgus macaques. J Virol85:4898–4909 [CrossRef][PubMed]
    [Google Scholar]
  16. Hahon N.. 1961; Smallpox and related poxvirus infections in the simian host. Bacteriol Rev25:459–476[PubMed]
    [Google Scholar]
  17. Haley P. J., Muggenburg B. A., Rebar A. H., Shopp G. M., Bice D. E.. 1989; Bronchoalveolar lavage cytology in cynomolgus monkeys and identification of cytologic alterations following sequential saline lavage. Vet Pathol26:265–273 [CrossRef][PubMed]
    [Google Scholar]
  18. Harris N., Buller R. M., Karupiah G.. 1995; Gamma interferon-induced, nitric oxide-mediated inhibition of vaccinia virus replication. J Virol69:910–915[PubMed]
    [Google Scholar]
  19. Hartings J. M., Roy C. J.. 2004; The automated bioaerosol exposure system: preclinical platform development and a respiratory dosimetry application with nonhuman primates. J Pharmacol Toxicol Methods49:39–55 [CrossRef][PubMed]
    [Google Scholar]
  20. Hinds W. C.. 1999; Respiratory Deposition, Aerosol Technology. Properties, Behavior and Measurement of Aerosol Particles New York: John Wiley & Sons;
    [Google Scholar]
  21. Huggins J., Goff A., Hensley L., Mucker E., Shamblin J., Wlazlowski C., Johnson W., Chapman J., Larsen T. et al. 2009; Nonhuman primates are protected from smallpox virus or monkeypox virus challenges by the antiviral drug ST-246. Antimicrob Agents Chemother53:2620–2625 [CrossRef][PubMed]
    [Google Scholar]
  22. Jahrling P. B., Hensley L. E., Martinez M. J., LeDuc J. W., Rubins K. H., Relman D. A., Huggins J. W.. 2004; Exploring the potential of variola virus infection of cynomolgus macaques as a model for human smallpox. Proc Natl Acad Sci U S A101:15196–15200 [CrossRef]
    [Google Scholar]
  23. Jahrling P. B., Tomori O.. 2014; Variola virus archives: a new century, a new approach. The Lancet383:1525–1526 [CrossRef]
    [Google Scholar]
  24. Johnson R. F., Dyall J., Ragland D. R., Huzella L., Byrum R., Jett C., St Claire M., Smith A. L., Paragas J. et al. 2011a; Comparative analysis of monkeypox virus infection of cynomolgus macaques by the intravenous or intrabronchial inoculation route. J Virol85:2112–2125 [CrossRef][PubMed]
    [Google Scholar]
  25. Johnson R. F., Yellayi S., Cann J. A., Johnson A., Smith A. L., Paragas J., Jahrling P. B., Blaney J. E.. 2011b; Cowpox virus infection of cynomolgus macaques as a model of hemorrhagic smallpox. Virology418:102–112 [CrossRef]
    [Google Scholar]
  26. Johnson R. F., Hammoud D. A., Lackemeyer M. G., Yellayi S., Solomon J., Bohannon J. K., Janosko K. B., Jett C., Cooper K. et al. 2015; Small particle aerosol inoculation of cowpox Brighton Red in rhesus monkeys results in a severe respiratory disease. Virology481:124–135 [CrossRef]
    [Google Scholar]
  27. Kramski M., Mätz-Rensing K., Stahl-Hennig C., Kaup F. J., Nitsche A., Pauli G., Ellerbrok H.. 2010; A novel highly reproducible and lethal nonhuman primate model for orthopox virus infection. PLoS One5:e10412 [CrossRef][PubMed]
    [Google Scholar]
  28. Mätz-Rensing K., Ellerbrok H., Ehlers B., Pauli G., Floto A., Alex M., Czerny C. P., Kaup F. J.. 2006; Fatal poxvirus outbreak in a colony of New World monkeys. Vet Pathol43:212–218 [CrossRef][PubMed]
    [Google Scholar]
  29. Milton D. K.. 2012; What was the primary mode of smallpox transmission? Implications for biodefense. Front Cell Infect Microbiol2: [CrossRef][PubMed]
    [Google Scholar]
  30. Mitra A. C., Sarkar J. K., Mukherjee M. K.. 1974; Virus content of smallpox scabs. Bull World Health Organ51:106–107[PubMed]
    [Google Scholar]
  31. Nalca A., Livingston V. A., Garza N. L., Zumbrun E. E., Frick O. M., Chapman J. L., Hartings J. M.. 2010; Experimental infection of cynomolgus macaques (Macaca fascicularis) with aerosolized monkeypox virus. PLoS One5:e12880 [CrossRef][PubMed]
    [Google Scholar]
  32. Parker A. K., Parker S., Yokoyama W. M., Corbett J. A., Buller R. M. L.. 2007a; Induction of natural killer cell responses by ectromelia virus controls infection. J Virol81:4070–4079 [CrossRef]
    [Google Scholar]
  33. Parker S., Nuara A., Buller R. M. L., Schultz D. A.. 2007b; Human monkeypox: an emerging zoonotic disease. Future Microbiol2:17–34 [CrossRef]
    [Google Scholar]
  34. Rao A. R., Jacob E. S., Kamalakshi S., Appaswamy S., Bradbury. 1968; Epidemiological studies in smallpox. A study of intrafamilial transmission in a series of 254 infected families. Indian J Med Res56:1826–1854[PubMed]
    [Google Scholar]
  35. 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 Dis194:773–780 [CrossRef][PubMed]
    [Google Scholar]
  36. Smith A. L., St Claire M., Yellayi S., Bollinger L., Jahrling P. B., Paragas J., Blaney J. E., Johnson R. F.. 2012; Intrabronchial inoculation of cynomolgus macaques with cowpox virus. J Gen Virol93:159–164 [CrossRef][PubMed]
    [Google Scholar]
  37. Sofi Ibrahim M., Kulesh D. A., Saleh S. S., Damon I. K., Esposito J. J., Schmaljohn A. L., Jahrling P. B.. 2003; Real-time PCR assay to detect smallpox virus. J Clin Microbiol41:3835–3839 [CrossRef][PubMed]
    [Google Scholar]
  38. Solomon J., Johnson R., Douglas D., Hammoud D.. 2014; New image analysis technique for quantitative longitudinal assessment of lung pathology on CT in infected rhesus macaques. In IEEE Computer-Based Medical Systems , p.169 Edited by O'Conner L.. New York: IEEE Computer Society;
    [Google Scholar]
  39. Tucker J. B.. 2011; Breaking the deadlock over destruction of the smallpox virus stocks. Biosecur Bioterror9:55–67 [CrossRef][PubMed]
    [Google Scholar]
  40. Von Essen S. G., Robbins R. A., Spurzem J. R., Thompson A. B., McGranaghan S. S., Rennard S. I.. 1991; Bronchoscopy with bronchoalveolar lavage causes neutrophil recruitment to the lower respiratory tract. Am Rev Respir Dis144:848–854 [CrossRef][PubMed]
    [Google Scholar]
  41. Vorou R. M., Papavassiliou V. G., Pierroutsakos I. N.. 2008; Cowpox virus infection: an emerging health threat. Curr Opin Infect Dis21:153–156 [CrossRef][PubMed]
    [Google Scholar]
  42. Wehrle P. F., Posch J., Richter K. H., Henderson D. A.. 1970; An airborne outbreak of smallpox in a German hospital and its significance with respect to other recent outbreaks in Europe. Bull World Health Organ43:669–679[PubMed]
    [Google Scholar]
  43. 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 Invest81:1581–1600 [CrossRef][PubMed]
    [Google Scholar]
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