Aerosol and Nasal Transmission of Chronic Wasting Disease in Cervidized Mice
Nathaniel D Denkers1, Davis M Seelig1, Glenn C. Telling2 and Edward A Hoover, Jr1,3
1 Colorado State University; 2 University of Kentucky Medical Center
3 E-mail: firstname.lastname@example.org
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 (dpi) and by examination of tissues for lesions and PrPCWD 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 7 aerosol-exposed Tg(cerPrP) mice developed clinical signs of neurologic dysfunction mandating euthanasia between 411 and 749 dpi. In all these mice, CWD infection was confirmed by detection of spongiform lesions and PrPCWD in the brain. Two of 9 intra-nasally inoculated Tg(cerPrP) mice also developed TSE associated with PrPCWD between 417 and 755 dpi. 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.
Received 30 October 2009; accepted 15 February 2010.