1887

Abstract

Little is known regarding the potential risk posed by aerosolized prions. Chronic wasting disease (CWD) is transmitted horizontally, almost surely by mucosal exposure, and CWD prions are present in saliva and urine of infected animals. However, whether CWD may be transmissible by the aerosol or nasal route is not known. To address this question, FVB mice transgenetically expressing the normal cervid PrP protein [Tg(cerPrP) mice] were exposed to CWD prions by either nose-only aerosol exposure or by drop-wise instillation into the nostrils. Mice were monitored for signs of disease for up to 755 days post-inoculation (p.i.) and by examination of tissues for lesions and PrP after necropsy. In particular, nasal mucosa, vomeronasal organ, lungs, lymphoid tissue and the brain were assessed for PrP by Western blotting and immunohistochemistry. Six of seven aerosol-exposed Tg(cerPrP) mice developed clinical signs of neurological dysfunction mandating euthanasia between 411 and 749 days p.i. In all these mice, CWD infection was confirmed by detection of spongiform lesions and PrP in the brain. Two of nine intranasally inoculated Tg(cerPrP) mice also developed transmissible spongiform encephalopathy associated with PrP between 417 and 755 days p.i. No evidence of PrP was detected in CWD-inoculated Tg(cerPrP) mice examined at pre-terminal time points. These results demonstrate that CWD can be transmitted by aerosol (as well as nasal) exposure and suggest that exposure via the respiratory system merits consideration for prion disease transmission and biosafety.

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2010-06-01
2019-08-23
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References

  1. Beekes, M. & McBride, P. A. ( 2000; ). Early accumulation of pathological PrP in the enteric nervous system and gut-associated lymphoid tissue of hamsters orally infected with scrapie. Neurosci Lett 278, 181–184.[CrossRef]
    [Google Scholar]
  2. Bessen, R. A., Martinka, S., Kelly, J. & Gonzalez, D. ( 2009; ). Role of the lymphoreticular system in prion neuroinvasion from the oral and nasal mucosa. J Virol 83, 6435–6445.[CrossRef]
    [Google Scholar]
  3. Browning, S. R., Mason, G. L., Seward, T., Green, M., Eliason, G. A., Mathiason, C., Miller, M. W., Williams, E. S., Hoover, E. & Telling, G. C. ( 2004; ). Transmission of prions from mule deer and elk with chronic wasting disease to transgenic mice expressing cervid PrP. J Virol 78, 13345–13350.[CrossRef]
    [Google Scholar]
  4. Buck, L. & Axel, R. ( 1991; ). A novel multigene family may encode odorant receptors: a molecular basis for odor recognition. Cell 65, 175–187.[CrossRef]
    [Google Scholar]
  5. DeJoia, C., Moreaux, B., O'Connell, K. & Bessen, R. A. ( 2006; ). Prion infection of oral and nasal mucosa. J Virol 80, 4546–4556.[CrossRef]
    [Google Scholar]
  6. Doving, K. B. & Trotier, D. ( 1998; ). Structure and function of the vomeronasal organ. J Exp Biol 201, 2913–2925.
    [Google Scholar]
  7. Dube, C., Mehren, K. G., Barker, I. K., Peart, B. L. & Balachandran, A. ( 2006; ). Retrospective investigation of chronic wasting disease of cervids at the Toronto Zoo, 1973–2003. Can Vet J 47, 1185–1193.
    [Google Scholar]
  8. Dulac, C. ( 2000; ). Sensory coding of pheromone signals in mammals. Curr Opin Neurobiol 10, 511–518.[CrossRef]
    [Google Scholar]
  9. Fox, K. A., Jewell, J. E., Williams, E. S. & Miller, M. W. ( 2006; ). Patterns of PrPCWD accumulation during the course of chronic wasting disease infection in orally inoculated mule deer (Odocoileus hemionus). J Gen Virol 87, 3451–3461.[CrossRef]
    [Google Scholar]
  10. Haley, N. J., Seelig, D. M., Zabel, M. D., Telling, G. C. & Hoover, E. A. ( 2009; ). Detection of CWD prions in urine and saliva of deer by transgenic mouse bioassay. PLoS One 4, e4848 [CrossRef]
    [Google Scholar]
  11. Hamir, A. N., Kunkle, R. A., Richt, J. A., Miller, J. M. & Greenlee, J. J. ( 2008; ). Experimental transmission of US scrapie agent by nasal, peritoneal, and conjunctival routes to genetically susceptible sheep. Vet Pathol 45, 7–11.[CrossRef]
    [Google Scholar]
  12. Heggebo, R., Press, C. M., Gunnes, G., Gonzalez, L. & Jeffrey, M. ( 2002; ). Distribution and accumulation of PrP in gut-associated and peripheral lymphoid tissue of scrapie-affected Suffolk sheep. J Gen Virol 83, 479–489.
    [Google Scholar]
  13. Heritage, P. L., Underdown, B. J., Arsenault, A. L., Snider, D. P. & McDermott, M. R. ( 1997; ). Comparison of murine nasal-associated lymphoid tissue and Peyer's patches. Am J Respir Crit Care Med 156, 1256–1262.[CrossRef]
    [Google Scholar]
  14. Hinds, W. C. ( 1999; ). Aerosol Technology: Properties, Behavior, and Measurement of Airborne Particles. New York: Wiley Interscience.
  15. Johnson, C. J., Phillips, K. E., Schramm, P. T., McKenzie, D., Aiken, J. M. & Pedersen, J. A. ( 2006; ). Prions adhere to soil minerals and remain infectious. PLoS Pathog 2, e32 [CrossRef]
    [Google Scholar]
  16. Kariv-Inbal, Z., Ben-Hur, T., Grigoriadis, N. C., Engelstein, R. & Gabizon, R. ( 2006; ). Urine from scrapie-infected hamsters comprises low levels of prion infectivity. Neurodegener Dis 3, 123–128.[CrossRef]
    [Google Scholar]
  17. Keane, D. P., Barr, D. J., Keller, J. E., Hall, S. M., Langenberg, J. A. & Bochsler, P. N. ( 2008; ). Comparison of retropharyngeal lymph node and obex region of the brainstem in detection of chronic wasting disease in white-tailed deer (Odocoileus virginianus). J Vet Diagn Invest 20, 58–60.[CrossRef]
    [Google Scholar]
  18. Kelliher, K. R., Baum, M. J. & Meredith, M. ( 2001; ). The ferret's vomeronasal organ and accessory olfactory bulb: effect of hormone manipulation in adult males and females. Anat Rec 263, 280–288.[CrossRef]
    [Google Scholar]
  19. Kim, T. Y., Shon, H. J., Joo, Y. S., Mun, U. K., Kang, K. S. & Lee, Y. S. ( 2005; ). Additional cases of chronic wasting disease in imported deer in Korea. J Vet Med Sci 67, 753–759.[CrossRef]
    [Google Scholar]
  20. Kincaid, A. E. & Bartz, J. C. ( 2007; ). The nasal cavity is a route for prion infection in hamsters. J Virol 81, 4482–4491.[CrossRef]
    [Google Scholar]
  21. Klemens, J. J., Kirtsreesakul, V., Luxameechanporn, T. & Naclerio, R. M. ( 2005; ). Acute bacterial rhinosinusitis causes hyperresponsiveness to histamine challenge in mice. Arch Otolaryngol Head Neck Surg 131, 905–910.[CrossRef]
    [Google Scholar]
  22. Kuper, C. F., Koornstra, P. J., Hameleers, D. M., Biewenga, J., Spit, B. J., Duijvestijn, A. M., van Breda Vriesman, P. J. & Sminia, T. ( 1992; ). The role of nasopharyngeal lymphoid tissue. Immunol Today 13, 219–224.[CrossRef]
    [Google Scholar]
  23. Mathiason, C. K., Powers, J. G., Dahmes, S. J., Osborn, D. A., Miller, K. V., Warren, R. J., Mason, G. L., Hays, S. A., Hayes-Klug, J. & other authors ( 2006; ). Infectious prions in the saliva and blood of deer with chronic wasting disease. Science 314, 133–136.[CrossRef]
    [Google Scholar]
  24. Meredith, M. & O'Connell, R. J. ( 1979; ). Efferent control of stimulus access to the hamster vomeronasal organ. J Physiol 286, 301–316.[CrossRef]
    [Google Scholar]
  25. Miller, M. W. & Williams, E. S. ( 2003; ). Prion disease: horizontal prion transmission in mule deer. Nature 425, 35–36.[CrossRef]
    [Google Scholar]
  26. Press, C. M., Heggebo, R. & Espenes, A. ( 2004; ). Involvement of gut-associated lymphoid tissue of ruminants in the spread of transmissible spongiform encephalopathies. Adv Drug Deliv Rev 56, 885–899.[CrossRef]
    [Google Scholar]
  27. Sbriccoli, M., Cardone, F., Valanzano, A., Lu, M., Graziano, S., De Pascalis, A., Ingrosso, L., Zanusso, G., Monaco, S., Bentivoglio, M. & Pocchiari, M. ( 2008; ). Neuroinvasion of the 263K scrapie strain after intranasal administration occurs through olfactory-unrelated pathways. Acta Neuropathologica 117, 175–184.
    [Google Scholar]
  28. Shaw, I. C. ( 1995; ). BSE and farmworkers. Lancet 346, 1365
    [Google Scholar]
  29. Sigurdson, C. J., Williams, E. S., Miller, M. W., Spraker, T. R., O'Rourke, K. I. & Hoover, E. A. ( 1999; ). Oral transmission and early lymphoid tropism of chronic wasting disease PrPres in mule deer fawns (Odocoileus hemionus). J Gen Virol 80, 2757–2764.
    [Google Scholar]
  30. Silveira, J. R., Raymond, G. J., Hughson, A. G., Race, R. E., Sim, V. L., Hayes, S. F. & Caughey, B. ( 2005; ). The most infectious prion protein particles. Nature 437, 257–261.[CrossRef]
    [Google Scholar]
  31. Spraker, T. R., Miller, M. W., Williams, E. S., Getzy, D. M., Adrian, W. J., Schoonveld, G. G., Spowart, R. A., O'Rourke, K. I., Miller, J. M. & Merz, P. A. ( 1997; ). Spongiform encephalopathy in free-ranging mule deer (Odocoileus hemionus), white-tailed deer (Odocoileus virginianus) and Rocky Mountain elk (Cervus elaphus nelsoni) in northcentral Colorado. J Wildl Dis 33, 1–6.[CrossRef]
    [Google Scholar]
  32. Spraker, T. R., Zink, R. R., Cummings, B. A., Sigurdson, C. J., Miller, M. W. & O'Rourke, K. I. ( 2002a; ). Distribution of protease-resistant prion protein and spongiform encephalopathy in free-ranging mule deer (Odocoileus hemionus) with chronic wasting disease. Vet Pathol 39, 546–556.[CrossRef]
    [Google Scholar]
  33. Spraker, T. R., Zink, R. R., Cummings, B. A., Wild, M. A., Miller, M. W. & O'Rourke, K. I. ( 2002b; ). Comparison of histological lesions and immunohistochemical staining of proteinase-resistant prion protein in a naturally occurring spongiform encephalopathy of free-ranging mule deer (Odocoileus hemionus) with those of chronic wasting disease of captive mule deer. Vet Pathol 39, 110–119.[CrossRef]
    [Google Scholar]
  34. Spraker, T. R., Balachandran, A., Zhuang, D. & O'Rourke, K. I. ( 2004; ). Variable patterns of distribution of PrPCWD in the obex and cranial lymphoid tissues of Rocky Mountain elk (Cervus elaphus nelsoni) with subclinical chronic wasting disease. Vet Rec 155, 295–302.[CrossRef]
    [Google Scholar]
  35. Thorne, N. & Amrein, H. ( 2003; ). Vomeronasal organ: pheromone recognition with a twist. Curr Biol 13, R220–R222.[CrossRef]
    [Google Scholar]
  36. van Keulen, L. J., Bossers, A. & van Zijderveld, F. ( 2008; ). TSE pathogenesis in cattle and sheep. Vet Res 39, 24 [CrossRef]
    [Google Scholar]
  37. Williams, E. S. ( 2005; ). Chronic wasting disease. Vet Pathol 42, 530–549.[CrossRef]
    [Google Scholar]
  38. Williams, E. S. & Young, S. ( 1992; ). Spongiform encephalopathies in Cervidae. Rev Sci Tech 11, 551–567.
    [Google Scholar]
  39. Williams, E. S. & Young, S. ( 1993; ). Neuropathology of chronic wasting disease of mule deer (Odocoileus hemionus) and elk (Cervus elaphus nelsoni). Vet Pathol 30, 36–45.[CrossRef]
    [Google Scholar]
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