PrPCWD lymphoid cell targets in early and advanced chronic wasting disease of mule deer

C.J. Sigurdson, C. Barillas-Mury, M.W. Miller, B. Oesch, L.J.M. van Keulen, J.P.M. Langeveld, E.A. Hoover

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    Abstract

    Up to 15% of free-ranging mule deer in northeastern Colorado and southeastern Wyoming, USA, are afflicted with a prion disease, or transmissible spongiform encephalopathy (TSE), known as chronic wasting disease (CWD). CWD is similar to a subset of TSEs including scrapie and variant Creutzfeldt¿Jakob disease in which the abnormal prion protein isoform, PrPCWD, accumulates in lymphoid tissue. Experimental scrapie studies have indicated that this early lymphoid phase is an important constituent of prion replication interposed between mucosal entry and central nervous system accumulation. To identify the lymphoid target cells associated with PrPCWD, we used triple-label immunofluorescence and high-resolution confocal microscopy on tonsils from naturally infected deer in advanced disease. We detected PrPCWD primarily extracellularly in association with follicular dendritic and B cell membranes as determined by frequent co-localization with antibodies against membrane bound immunoglobulin and CD21. There was minimal co-localization with cytoplasmic labels for follicular dendritic cells (FDC). This finding could indicate FDC capture of PrPCWD, potentially in association with immunoglobulin or complement, or PrPC conversion on FDC. In addition, scattered tingible body macrophages in the germinal centre contained coarse intracytoplasmic aggregates of PrPCWD, reflecting either phagocytosis of PrPCWD on FDC processes, apoptotic FDC or B cells, or actual PrPCWD replication within tingible body macrophages. To compare lymphoid cell targets in early and advanced disease, we also examined: (i) PrPCWD distribution in lymphoid cells of fawns within 3 months of oral CWD exposure and (ii) tonsil biopsies from preclinical deer with naturally acquired CWD. These studies revealed that the early lymphoid cellular distribution of PrPCWD was similar to that in advanced disease, i.e. in a pattern suggesting FDC association. We conclude that in deer, PrPCWD accumulates primarily extracellularly and associated with FDCs and possibly B cells ¿ a finding which raises questions as to the cells responsible for pathological prion production
    Original languageEnglish
    Pages (from-to)2617-2628
    JournalJournal of General Virology
    Volume83
    Issue number10
    DOIs
    Publication statusPublished - 2002

    Keywords

    • follicular dendritic cells
    • creutzfeldt-jakob-disease
    • immunodeficiency-virus type-1
    • spongiform encephalopathy bse
    • cervus-elaphus-nelsoni
    • prion protein
    • monoclonal-antibody
    • odocoileus-hemionus
    • natural scrapie
    • immunohistochemical detection

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  • Cite this

    Sigurdson, C. J., Barillas-Mury, C., Miller, M. W., Oesch, B., van Keulen, L. J. M., Langeveld, J. P. M., & Hoover, E. A. (2002). PrPCWD lymphoid cell targets in early and advanced chronic wasting disease of mule deer. Journal of General Virology, 83(10), 2617-2628. https://doi.org/10.1099/0022-1317-83-10-2617