The Identification of Differentially Expressed Genes in Nasal Swabs from Chronic Wasting Disease-Infected White-tailed Deer

Abstract

Chronic wasting disease (CWD) is a transmissible spongiform encephalopathy (TSE) or prion disease, which is spreading in cervid populations, including mule deer (Odocoileus hemionus), white-tailed deer (Odocoileus virginianus), and Rocky Mountain elk (Cervus elaphus nelsoni). The pathogen of CWD is the abnormally misfolded prion protein (PrPsc) which is converted from normal function cellular prion protein (PrPc). PrPc is coded by the PRNP gene, which is highly expressed in the central nervous system (CNS) and also expressed in the peripheral nervous system. The specific biological function of PrPc in CNS still remains unclear, and the pathogenesis of the PrPsc also needs a better understanding. CWD is spreading fast in many places around the world, and CWD is fatal to all infected animals with no treatment or vaccine for it. Our final goal of this research is to develop a diagnosis and treatment approach for CWD. I hypothesize that there are differentially expressed genes (DEGs) caused by CWD in the nasal brush samples, and the identified DEGs could be used for CWD diagnosis. This study used next-generation total RNA sequencing to identify potential biomarkers in nasal swab samples from CWD white-tailed deer and increase understanding of CWD pathogenesis. We annotated and filtered genes from the reference genome and identified DEGs consistently altered in late-stage post-infection samples. Additionally, we performed Gene Set Enrichment Analysis for these identified genes at each time point, and we found cell proliferation pathways were suppressed, and immune response pathways were activated post-CWD infection. These biomarkers and pathways could provide some new insights into CWD diagnosis and CWD treatment for future research.