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Permanent URL to this publication: http://dx.doi.org/10.5167/uzh-1907

Kaeser, P S; Klein, M A; Schwarz, P; Aguzzi, A (2001). Efficient lymphoreticular prion propagation requires PrP(c) in stromal and hematopoietic cells. Journal of Virology, 75(15):7097-7106.

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Abstract

In most prion diseases, infectivity accumulates in lymphoreticular organs early after infection. Defects in hematopoietic compartments, such as impaired B-cell maturation, or in stromal compartments, such as abrogation of follicular dendritic cells, can delay or prevent lymphoreticular prion colonization. However, the nature of the compartment in which prion replication takes place is controversial, and it is unclear whether this compartment coincides with that expressing the normal prion protein (PrP(c)). Here we studied the distribution of infectivity in splenic fractions of wild-type and fetal liver chimeric mice carrying the gene that encodes PrP(c) (Prnp) solely on hematopoietic or on stromal cells. We fractionated spleens at various times after intraperitoneal challenge with prions and assayed infectivity by bioassay. Upon high-dose challenge, chimeras carrying PrP(c) on hematopoietic cells accumulated prions in stroma and in purified splenocytes. In contrast, after low-dose challenge ablation of Prnp in either compartment prevented splenic accumulation of infectivity, indicating that optimal prion replication requires PrP(c) expression by both stromal and hematopoietic compartments.

Item Type:Journal Article, refereed
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Institute of Neuropathology
DDC:570 Life sciences; biology
610 Medicine & health
Language:English
Date:1 August 2001
Deposited On:11 Feb 2008 12:26
Last Modified:28 Nov 2013 01:57
Publisher:American Society for Microbiology
ISSN:0022-538X
Publisher DOI:10.1128/JVI.75.15.7097-7106.2001
PubMed ID:11435590
Citations:Web of Science®. Times Cited: 54
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