1887

Abstract

We previously demonstrated that small-particle (0.5–3.0 µm) aerosol infection of rhesus monkeys (Macaca mulatta) 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 ( Johnson et al., 2015 ). 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.

Loading

Article metrics loading...

/content/journal/jgv/10.1099/jgv.0.000501
2016-08-01
2019-10-20
Loading full text...

Full text loading...

/deliver/fulltext/jgv/97/8/1942.html?itemId=/content/journal/jgv/10.1099/jgv.0.000501&mimeType=html&fmt=ahah

References

  1. Aebersold P..( 2012;). FDA experience with medical countermeasures under the Animal Rule. . Adv Prev Med 2012: 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 Virol 84: 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. . Virology 334: 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 Microbiol 2: 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 Toxicol 27: 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 Immunol 164: 3246–3254. [CrossRef] [PubMed]
    [Google Scholar]
  7. Bray M., Buller M..( 2004;). Looking back at smallpox. . Clin Infect Dis 38: 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 Pathog 10: 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 Hyg 67: 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 Virol 86: 9105–9112. [CrossRef] [PubMed]
    [Google Scholar]
  12. Fenner F..( 1980;). Smallpox and its eradication. . Aust Nz J Med 10: 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 Virol 85: 4898–4909. [CrossRef] [PubMed]
    [Google Scholar]
  16. Hahon N..( 1961;). Smallpox and related poxvirus infections in the simian host. . Bacteriol Rev 25: 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 Pathol 26: 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 Virol 69: 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 Methods 49: 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 Chemother 53: 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 A 101: 15196–15200. [CrossRef]
    [Google Scholar]
  23. Jahrling P. B., Tomori O..( 2014;). Variola virus archives: a new century, a new approach. . The Lancet 383: 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 Virol 85: 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. . Virology 418: 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. . Virology 481: 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 One 5: 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 Pathol 43: 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 Microbiol 2:. [CrossRef] [PubMed]
    [Google Scholar]
  30. Mitra A. C., Sarkar J. K., Mukherjee M. K..( 1974;). Virus content of smallpox scabs. . Bull World Health Organ 51: 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 One 5: 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 Virol 81: 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 Microbiol 2: 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 Res 56: 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 Dis 194: 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 Virol 93: 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 Microbiol 41: 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 Bioterror 9: 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 Dis 144: 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 Dis 21: 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 Organ 43: 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 Invest 81: 1581–1600. [CrossRef] [PubMed]
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/jgv.0.000501
Loading
/content/journal/jgv/10.1099/jgv.0.000501
Loading

Data & Media loading...

Supplements

Supplementary File 1



PDF

Most Cited This Month

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error