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Journal of Virology, August 2001, p. 7097-7106, Vol. 75, No. 15
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.15.7097-7106.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Efficient Lymphoreticular Prion Propagation Requires PrPc in Stromal and Hematopoietic Cells

Pascal S. Kaeser, Michael A. Klein,dagger Petra Schwarz, and Adriano Aguzzi*

Institute of Neuropathology, University Hospital, 8091 Zurich, Switzerland

Received 8 March 2001/Accepted 2 May 2001

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 (PrPc). Here we studied the distribution of infectivity in splenic fractions of wild-type and fetal liver chimeric mice carrying the gene that encodes PrPc (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 PrPc 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 PrPc expression by both stromal and hematopoietic compartments.

* Corresponding author. Mailing address: Institut für Neuropathologie, UniversitätsSpital Zürich, Schmelzbergstr. 12, CH-8091 Zürich, Switzerland. Phone: 41 (01) 255 2869. Fax: 41 (01) 255 4402. E-mail: adriano{at}pathol.unizh.ch.

dagger Present address: Institute of Pathology, CH-4003 Basel, Switzerland.

Journal of Virology, August 2001, p. 7097-7106, Vol. 75, No. 15
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.15.7097-7106.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


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