Small-Ruminant Lentivirus Enhances PrPSc Accumulation in Cultured Sheep Microglial Cells

James B Stanton; Donald P Knowles; Katherine I O'Rourke; Lynn M Herrmann-Hoesing; Bruce A Mathison; Timothy V Baszler

doi:10.1128/JVI.01137-08

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Small-Ruminant Lentivirus Enhances PrPSc Accumulation in Cultured Sheep Microglial Cells

Journal article

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Small-Ruminant Lentivirus Enhances PrPSc Accumulation in Cultured Sheep Microglial Cells

James B Stanton, Donald P Knowles, Katherine I O'Rourke, Lynn M Herrmann-Hoesing, Bruce A Mathison and Timothy V Baszler

Journal of virology, Vol.82(20), pp.9839-9847

10/2008

DOI: https://doi.org/10.1128/JVI.01137-08

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https://hdl.handle.net/2376/104232

PMCID: PMC2566263

PMID: 18684809

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https://doi.org/10.1128/JVI.01137-08View

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Abstract

Virus-Cell Interactions

Sheep scrapie is the prototypical transmissible spongiform encephalopathy (prion disease), which has a fundamental pathogenesis involving conversion of normal cellular prion protein (PrP C [C superscript stands for cellular]) to disease-associated prion protein (PrP Sc [Sc superscript stands for sheep scrapie]). Sheep microglial cell cultures, derived from a prnp 136VV/171QQ near-term fetal brain, were developed to study sheep scrapie in the natural host and to investigate potential cofactors in the prion conversion process. Two culture systems, a primary cell culture and a cell line transformed with the large T antigen of simian virus 40, were developed, and both were identified as microglial in origin as indicated by expression of several microglial phenotype markers. Following exposure to PrP Sc , sheep microglial cells demonstrated relatively low levels (transformed cell line) to high levels (primary cell line) of PrP Sc accumulation over time. The accumulated PrP Sc demonstrated protease resistance, an inferred beta-sheet conformation (as determined by a commercial enzyme-linked immunosorbent assay), specific inhibition by anti-PrP antibodies, and was transmissible in a dose-dependent manner. Primary microglia coinfected with a small-ruminant lentivirus (caprine arthritis encephalitis virus-Cork strain) and PrP Sc demonstrated an approximately twofold increase in PrP Sc accumulation compared to that of primary microglia infected with PrP Sc alone. The results demonstrate the in vitro utility of PrP Sc -permissive sheep microglial cells in investigating the biology of natural prion diseases and show that small-ruminant lentiviruses enhance prion conversion in cultured sheep microglia.

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Title: Small-Ruminant Lentivirus Enhances PrPSc Accumulation in Cultured Sheep Microglial Cells
Creators: James B Stanton - Department of Veterinary Microbiology and Pathology, Washington State University, Pullman, Washington 99164
Donald P Knowles - Department of Veterinary Microbiology and Pathology, Washington State University, Pullman, Washington 99164
Katherine I O'Rourke - Department of Veterinary Microbiology and Pathology, Washington State University, Pullman, Washington 99164
Lynn M Herrmann-Hoesing - Department of Veterinary Microbiology and Pathology, Washington State University, Pullman, Washington 99164
Bruce A Mathison - Department of Veterinary Microbiology and Pathology, Washington State University, Pullman, Washington 99164
Timothy V Baszler - Department of Veterinary Microbiology and Pathology, Washington State University, Pullman, Washington 99164
Publication Details: Journal of virology, Vol.82(20), pp.9839-9847
Academic Unit: Veterinary Microbiology and Pathology, Department of; Paul G. Allen School for Global Animal Health
Publisher: American Society for Microbiology (ASM)
Identifiers: 99900546604201842
Language: English
Resource Type: Journal article