Aerosol and nasal transmission of chronic wasting disease in cervidized mice

Nathaniel D. Denkers, Davis M. Seelig, Glenn C. Telling, Edward A. Hoover

Research output: Contribution to journalArticle

42 Citations (Scopus)

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 PrPC 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 CWD after necropsy. In particular, nasal mucosa, vomeronasal organ, lungs, lymphoid tissue and the brain were assessed for PrPCWD 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 PrPCWD in the brain. Two of nine intranasally inoculated Tg(cerPrP) mice also developed transmissible spongiform encephalopathy associated with PrPCWD between 417 and 755 days p.i. No evidence of PrPCWD 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.

Original languageEnglish (US)
Pages (from-to)1651-1658
Number of pages8
JournalJournal of General Virology
Volume91
Issue number6
DOIs
StatePublished - Jun 1 2010

Fingerprint

Chronic Wasting Disease
Nasal Sprays
PrPC Proteins
Prions
Aerosols
Prion Diseases
Nose
Vomeronasal Organ
Euthanasia
Nasal Mucosa
Brain
Lymphoid Tissue
Saliva
Respiratory System
Western Blotting
Immunohistochemistry
Urine

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Aerosol and nasal transmission of chronic wasting disease in cervidized mice. / Denkers, Nathaniel D.; Seelig, Davis M.; Telling, Glenn C.; Hoover, Edward A.

In: Journal of General Virology, Vol. 91, No. 6, 01.06.2010, p. 1651-1658.

Research output: Contribution to journalArticle

Denkers, Nathaniel D. ; Seelig, Davis M. ; Telling, Glenn C. ; Hoover, Edward A. / Aerosol and nasal transmission of chronic wasting disease in cervidized mice. In: Journal of General Virology. 2010 ; Vol. 91, No. 6. pp. 1651-1658.
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