title: Induced prion protein controls immune-activated retroviruses in the mouse spleen.
abstract: The prion protein (PrP) is crucially involved in transmissible spongiform encephalopathies (TSE), but neither its exact role in disease nor its physiological function are known. Here we show for mice, using histological, immunochemical and PCR-based methods, that stimulation of innate resistance was followed by appearance of numerous endogenous retroviruses and ensuing PrP up-regulation in germinal centers of the spleen. Subsequently, the activated retroviruses disappeared in a PrP-dependent manner. Our results reveal the regular involvement of endogenous retroviruses in murine immune responses and provide evidence for an essential function of PrP in the control of the retroviral activity. The interaction between PrP and ubiquitous endogenous retroviruses may allow new interpretations of TSE pathophysiology and explain the evolutionary conservation of PrP.
authors.affiliation: Institute of Experimental Immunology, University of Zürich, Zürich, Switzerland. marius.loetscher@cslbehring.com
authors.forename: Marius
authors.initials: M
authors.lastname: Lötscher
authors.forename: Mike
authors.initials: M
authors.lastname: Recher
authors.forename: Karl S
authors.initials: KS
authors.lastname: Lang
authors.forename: Alexander
authors.initials: A
authors.lastname: Navarini
authors.forename: Lukas
authors.initials: L
authors.lastname: Hunziker
authors.forename: Roger
authors.initials: R
authors.lastname: Santimaria
authors.forename: Markus
authors.initials: M
authors.lastname: Glatzel
authors.forename: Petra
authors.initials: P
authors.lastname: Schwarz
authors.forename: Jürg
authors.initials: J
authors.lastname: Böni
authors.forename: Rolf M
authors.initials: RM
authors.lastname: Zinkernagel
mesh_terms: D000818:Animals; D001483:Base Sequence; D015153:Blotting, Western; D017931:DNA Primers; D007150:Immunohistochemistry; D051379:Mice; D008810:Mice, Inbred C57BL; D008856:Microscopy, Fluorescence; D011328:Prions / Q000502:physiology*; D012190:Retroviridae / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013154:Spleen / Q000276:immunology / Q000821:virology*; D014775:Virus Activation
chemical_list: D017931:DNA Primers; D011328:Prions