NR AWPN
AU Vaccari,G.; D'Agostino,C.; Conte,M.; Di Bari,M.A.; Borroni,R.; Marcon,S.; De Grossi,L.; Rosone,F.; Giordani,F.; Cosseddu,G.M.; Morelli,L.; Nonno,R.; Agrimi,U.
TI Protective effect of ARQK176, AT137RQ, AK142RQ and ARR PrP alleles in Sarda sheep experimentally infected with scrapie
QU International Conference - Prion 2006: Strategies, advances and trends towards protection of society - 3.10.-6.10.2006, Torino, Italy, Lingotto Conference Centre - Poster sessions GEN-28
PT Konferenz-Poster
AB The aim of this study is to investigate the susceptibility to scrapie infection of Sarda sheep carrying the most diffuse PrP alleles (ARQ, AHQ, ARH and ARR) and ARQ variants (AT137RQ, AK142RQ and ARQK176). Experimental infections were carried out using a well characterised isolate of natural scrapie from Italy. Preliminary results at 1300 and 1390 dpi are reported for intracerebral (i.c.) and oral challenge, respectively. Survival times after i.c. inoculation according to PrP genotype were: ARQ/ARQ (n=5/5) 462±25 dpi, ARQ/AHQ (5/5) 703±26 dpi, AHQ/AHQ (1/1) 790 dpi, ARQ/ARH (1/1) 1083 dpi and ARH/AHQ (3/3) 1252±88 dpi. None of the sheep carrying the ARQ/ARR (15), ARR/ARR (5), ARR/AHQ (1), ARR/ARH (1) genotypes showed clinical signs consistent with scrapie at time of writing. Interestingly, also sheep carrying additional mutations of the ARQ allele (one AT137RQ/ARQK176 and one ARQK176/AHQ) failed to show clinical signs despite their putative susceptibility according to 136, 154 and 171 codons. After oral infection, survival times were observed as follows: ARQ/ARQ (5/5) 832±54 dpi, ARQ/AHQ (5/5) 1115±59 dpi. None of the sheep with the ARQ/ARR (20), ARR/ARR (5), ARQ/ARH (3), ARR/ARH (1) genotypes showed clinical signs of scrapie, to date. Similarly to what observed in i.c. inoculation, sheep with additional mutations - ARQ/AT137RQ (3), ARQ/ARQK176 (1) and ARQ/AK142RQ (1) - are so far healthy. In a parallel study investigating the kinetics of PrPsc distribution in Sarda sheep after oral scrapie infection, individual animals with the ARQ/ARQK176, ARQ/AK142RQ and ARQ/AT137RQ genotypes, culled at 9, 12 and 20 months post infection (p.i.), respectively, were negative for PrPsc deposition, whereas ARQ/ARQ animals culled at the same intervals p.i. were positive in nervous and/or lymphoid tissues. The present study shows that susceptibility to scrapie in Sarda sheep is clearly governed by the PrP genotype and that the most susceptible alleles are in decreasing order, ARQ, AHQ and ARH. Preliminary results at 1300 d.p.i. indicate that the presence of at least one ARR allele could confers resistance to clinical scrapie. Unexpectedly, also single mutations on the susceptible ARQ allele would seem to confer protection to experimental scrapie infection.
AD G. Vaccari, C.D'Agostino, M. Conte, M.A. Di Bari, R. Borroni, S. Marcon, G.M. Cosseddu, L. Morelli, R. Nonno, U. Agrimi: Istituto Superiore di Sanità, Dep. Food Safety and Animal Health, Rome, Italy; L. De Grossi, F. Rosone, F. Giordani: Istituto Zooprofilattico Sperimentale del Lazio e della Toscana, Rome, Italy. E-mail: gvaccari@iss.it
SP englisch
PO Italien