In:
Journal of Virology, American Society for Microbiology, Vol. 78, No. 9 ( 2004-05), p. 4776-4782
Abstract:
Dendritic cells (DC) of the CD11c + myeloid phenotype have been implicated in the spread of scrapie in the host. Previously, we have shown that CD11c + DC can cause a rapid degradation of proteinase K-resistant prion proteins (PrP Sc ) in vitro, indicating a possible role of these cells in the clearance of PrP Sc . To determine the mechanisms of PrP Sc degradation, CD11c + DC that had been exposed to PrP Sc derived from a neuronal cell line (GT1-1) infected with scrapie (ScGT1-1) were treated with a battery of protease inhibitors. Following treatment with the cysteine protease inhibitors (2S,3S)- trans -epoxysuccinyl- l -leucylamido-3-methylbutane (E-64c), its ethyl ester (E-64d), and leupeptin, the degradation of PrP Sc was inhibited, while inhibitors of serine and aspartic and metalloproteases (aprotinin, pepstatin, and phosphoramidon) had no effect. An endogenous degradation of PrP Sc in ScGT1-1 cells was revealed by inhibiting the expression of cellular PrP (PrP C ) by RNA interference, and this degradation could also be inhibited by the cysteine protease inhibitors. Our data show that PrP Sc is proteolytically cleaved preferentially by cysteine proteases in both CD11c + DC and ScGT1-1 cells and that the degradation of PrP Sc by proteases is different from that of PrP C . Interference by protease inhibitors with DC-induced processing of PrP Sc has the potential to modify prion spread, clearance, and immunization in a host.
Type of Medium:
Online Resource
ISSN:
0022-538X
,
1098-5514
DOI:
10.1128/JVI.78.9.4776-4782.2004
Language:
English
Publisher:
American Society for Microbiology
Publication Date:
2004
detail.hit.zdb_id:
1495529-5
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