NR ABGZ
AU Beringue,V.; Lasmezas,C.I.; Adjou,K.T.; Demaimay,R.; Lamoury,F.; Deslys,J.P.; Seman,M.; Dormont,D.
TI Inhibiting scrapie neuroinvasion by polyene antibiotic treatment of SCID mice
QU Journal of General Virology 1999 Jul; 80(7): 1873-7
IA http://intl-vir.sgmjournals.org/cgi/content/abstract/80/7/1873
PT journal article
AB The polyene antibiotic MS-8209 is currently one of the most effective drugs in the treatment of experimental scrapie. However, its mechanism of action and its site of intervention in the pathogenetical process of scrapie infection are largely unknown. It has been shown previously that the infection of immunodeficient SCID mice by the peripheral route provides a reliable model for direct scrapie neuroinvasion, bypassing the lymphoreticular system. Indeed, a proportion of SCID mice develop scrapie after a similar time to immunocompetent mice, despite their severe immune impairment. This model is now used to clarify the targets of MS-8209. In SCID mice, MS-8209 treatment protected against infection but did not prolong survival time. In SCID mice immunologically reconstituted prior to inoculation, the drug delayed the disease without an effect on the attack rate. These findings strongly suggest that MS-8209 acts by hampering the first step of the neuroinvasion process, i.e. the uptake of the infectious agent by peripheral nerve endings. The mechanism leading to the inhibition of agent propagation to nervous cells is discussed with regard to the properties of polyene antibiotics.
ZR 26 Zitate
MH Amphotericin B/*analogs & derivatives/pharmacology/therapeutic use; Animals; Antiviral Agents/pharmacology/*therapeutic use; Mice; Mice, SCID; Nervous System/virology; Prions/*drug effects; Research Support, Non-U.S. Gov't; Scrapie/*prevention & control
AD CEA, Service de Neurovirologie, DSV/DRM, CRSSA, Fontenay aux Roses, France.
SP englisch
PO England