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Title:   Author  item
                                            HALEY, NICHOLAS - Kansas State Universityitem
                                            SIEPKER, CHRISTOPHER - Kansas State Universityitem
                                            Greenlee, Justinitem
                                            RICHT, JÜRGEN - Kansas State University
  Submitted to: Journal of General Virology
                                    Publication Type: Peer Reviewed Journal
                                    Publication Acceptance Date: 3/30/2016
                                    Publication  Date: 1/7/2016
                                    Citation: Haley, N.J., Siepker, C., Greenlee, J.J., Richt, J.A. 2016. Limited amplification of chronic wasting disease prions in the peripheral tissues of intracerebrally inoculated cattle. Journal of General Virology. 97:1720-1724.Interpretive Summary: Chronic Wasting Disease (CWD), a fatal neurodegenerative disease that occurs in farmed and wild cervids (deer and elk) of North America, is a transmissible spongiform encephalopathy (TSE). TSEs are caused by infectious proteins called prions that are resistant to various methods of decontamination and environmental degradation. Cattle could be exposed to chronic wasting disease (CWD) by contact with infected farmed or free-ranging cervids. The purpose of this study was to use an in vitro amplification method called real time quaking induced conversion (RT-QuIC) to assess tissues from cattle inoculated with CWD for low levels of prions not detected by traditional diagnostic methods such as western blot and immunohistochemistry. This study reports that prions were identified by RT-QuIC only in cattle that were confirmed positive by traditional methods. However, prions were rarely identified in some peripheral tissues such as mesenteric lymph node, tonsil, or nasal turbinate that were not considered positive by traditional methods. These results suggest that cattle experimentally inoculated with CWD may have some limited amount of prion infectivity outside of the brain and spinal cord that may represent a previously unrecognized risk for transmission. This information could have an impact on regulatory officials developing plans to reduce or eliminate TSEs and farmers with concerns about ranging cattle on areas where CWD may be present.
                                Technical Abstract: Chronic wasting disease (CWD) is a fatal neurodegenerative disease, classified as a prion disease or transmissible spongiform encephalopathy (TSE) similar to bovine spongiform encephalopathy (BSE). Cervids affected by CWD accumulate an abnormal protease resistant prion protein throughout the central nervous system (CNS), as well as in both lymphatic and excretory tissues – an aspect of prion disease pathogenesis not observed in cattle with BSE. Using seeded amplification through real time quaking induced conversion (RT-QuIC), we investigated whether the bovine host or prion agent was responsible for this aspect of TSE pathogenesis. We blindly examined numerous central and peripheral tissues from cattle inoculated with CWD for prion seeding activity. Seeded amplification was readily detected in the CNS, though rarely observed in peripheral tissues, with a limited distribution similar to that of BSE prions in cattle. This seems to indicate that prion peripheralization in cattle is a host-driven characteristic of TSE infection.


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