Induced prion protein controls immune-activated retroviruses in the mouse spleen.
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.
Lötscher
Marius
M
Institute of Experimental Immunology, University of Zürich, Zürich, Switzerland. marius.loetscher@cslbehring.com
Recher
Mike
M
Lang
Karl S
KS
Navarini
Alexander
A
Hunziker
Lukas
L
Santimaria
Roger
R
Glatzel
Markus
M
Schwarz
Petra
P
Böni
Jürg
J
Zinkernagel
Rolf M
RM
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
D017931:DNA Primers; D011328:Prions