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Journal of Virology, June 1999, p. 5089-5097, Vol. 73, No. 6
Section of Neuropathology, Yale School of
Medicine, New Haven, Connecticut 06510
Received 7 December 1998/Accepted 10 March 1999
Progressive changes in host mRNA expression can illuminate crucial
pathogenetic pathways in infectious disease. We examined general and
specific approaches to mRNA expression in three rodent models of
Creutzfeldt-Jakob disease (CJD). Each of these models displays
distinctive neuropathology. Although mRNAs for the chemokine receptor
CCR5, the lysosomal protease cathepsin S, and the pleiotropic cytokine
transforming growth factor
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.
Microglial Activation Varies in Different Models of
Creutzfeldt-Jakob Disease
1 (TGF-
1) were progressively upregulated in rodent CJD, the temporal patterns and peak magnitudes of
each of these transcripts varied substantially among models. Cathepsin
S and TGF-
1 were elevated more than 15-fold in mice and rats
infected with two different CJD strains, but not in CJD-infected hamsters. In rats, an early activation of microglial transcripts preceded obvious deposits of prion protein (PrP) amyloid. However, in
each of the three CJD models, the upregulation of CCR5, cathepsin S,
and TGF-
1 was variable with respect to the onset of PrP pathology. These results show glial cell involvement varies as a consequence of
the agent strain and species infected. Although neurons are generally
assumed to be the primary sites for agent replication and abnormal PrP
formation, microglia may be targeted by some agent strains. In such
instances, microglia can both process PrP to become amyloid and can
enhance neuronal destruction. Because microglia can participate in
agent clearance, they may also act as chronic reservoirs of
infectivity. Finally, the results here strongly suggest that TGF-
1
can be an essential signal for amyloid deposition.
*
Corresponding author. Mailing address: Yale School of
Medicine, 333 Cedar St., New Haven, CT 06510. Phone: (203) 785-4442. Fax: (203) 785-6381. E-mail: laura.manueldis{at}yale.edu.
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