NR AXQG

AU Kramer,M.L.; Bartz,J.C.

TI Transport and Clearance of Hamster-adapted Transmissible Mink Encephalopathy following Intraperitoneal Inoculation

QU International Conference - Prion 2007 (26.-28.9.2007) Edinburgh International Conference Centre, Edinburgh, Scotland, UK - Book of Abstracts: Pathology and Pathogenesis P03.158

IA http://www.prion2007.com/pdf/Prion Book of Abstracts.pdf

PT Konferenz-Poster

AB Background: Following peripheral routes of infection, the abnormal isoform of the prion protein (PrpSc) is initially detected in secondary lymphoreticular system (LRS) tissues. Prion replication within secondary LRS tissues is thought to aid in the efficiency of neuroinvasion. Intraperitoneal (i.p.) inoculation of the drowsy (DY) strain of hamsteradapted transmissible mink encephalopathy (TME) resulted in a failure to detect DY PrPsc in spleen, submandibular lymph node or mesenteric lymph node by Western blot analysis, immunohistochemistry or animal bioassay at 60 days post-infection.
Objectives: The aim of this study is to determine the distribution of PrPsc in secondary LRS tissues during the early stages of infection.
Methods: Following i.p. inoculation of the hyper (HY) and DY TME agents, peritoneal cells, medial iliac lymph node, mesenteric lymph node, and spleen were collected from 1 hour to 20 weeks post-infection. We have analyzed these tissues for the presence of PrPsc by Western blot analysis. We also employed a macrophage cell culture model system to study the uptake and degradation of PrPsc following TME infection of these cells.
Results: Following i.p. inoculation, HY PrPsc is present in the spleen, medial iliac lymph node, and mesenteric lymph node through 32 hours post-infection. DY PrPsc is detectable in the spleen and medial iliac lymph node through 4 hours and 32 hours post-infection, respectively. In all tissues, both HY and DY PrPsc fall below the levels detectable by Western blot analysis by 64 hours post-infection. In the cell co-culture model system, PrPsc levels of the cells peak at 24 hours post-infection, while levels PrPsc in the media decrease through 72 hours post-infection.
Conclusion: HY and DY PrPsc are detected in secondary LRS tissue at early time points post-infection, indicating that both agents are transported to these tissues. We have also studied degradation of PrPsc using an in vitro macrophage model. We have shown that there is no significant difference between HY and DY PrPsc uptake and degradation in this model system. These combined findings suggest that the inability of DY TME to cause disease following i.p. inoculation may be a result of retention and/or replication within secondary LRS tissues.

AD M. Kramer, J. Bartz, Creighton University, Department of Medical Microbiology and Immunology, USA

SP englisch

PO Schottland

EA pdf-Datei und Poster

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