Mother to Offspring Transmission of Chronic Wasting Disease

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DESCRIPTION (provided by applicant): Chronic wasting disease (CWD) is an emergent, efficiently transmitted, fatal prion disease of cervids (deer, elk, moose) that is now identified in 17 states, 2 Canadian provinces and 1 Asian country. Epidemiological studies in deer suggest that CWD is transmitted horizontally, yet surprisingly little is known about its potential vertical transmission. The question of whether and how CWD, and prions overall, are transmitted from mother to offspring forms the basis for this proposal. We propose to address two specific aims to assess whether vertical/maternal transmission may explain in large part the efficient spread of CWD in nature by employing a newly developed small cervid model of CWD infection in Reeve's muntjac deer, which are readily housed and bred in indoor facilities. We will employ CWD- infected pregnant female muntjac deer and their offspring to determine whether and how infectious CWD prions are transmitted in utero/prenatally and/or postnatally via milk or maternal saliva. Due to uncertainties regarding the nature of prion state and transfer, we will use several assays to detect CWD prions--including direct immunoassays, serial protein misfolding cyclic amplification (sPMCA) and transgenic mouse bioassay. The goal of this work is to determine the most significant pathway whereby CWD prions are transferred from mother to offspring, and thereby to gain insight into the mechanisms of vertical prion transmission overall.