- J.C. Espinosa (2)
- C. Fast (1)
- W. Goldmann (1)
- M.H. Groschup (1)
- A. Gutiérrez-Adán (1)
- J.P.M. Langeveld (1)
- A. Miranda (1)
- Nadeem Muhammad (1)
- B. Pintado (1)
- I. Prieto (1)
- Kerstin Tauscher (1)
- J.M. Torres (1)
Effect of Q211 and K222 PRNP polymorphic variants in the susceptibility of goats to oral infections with Goat Bovine Spongiform Encephalopathy
Aguilar-Calvo, Patricia ; Fast, C. ; Tauscher, Kerstin ; Espinosa, J.C. ; Groschup, M.H. ; Muhammad, Nadeem ; Goldmann, W. ; Langeveld, J.P.M. ; Bossers, A. ; Andreoletti, O. - \ 2015
The Journal of Infectious Diseases 212 (2015)4. - ISSN 0022-1899 - p. 664 - 672.
Background. The prion protein-encoding gene (PRNP) is one of the major determinants for scrapie occurrence in sheep and goats. However, its effect on bovine spongiform encephalopathy (BSE) transmission to goats is not clear.
Methods. Goats harboring wild-type, R/Q211 or Q/K222 PRNP genotypes were orally inoculated with a goat-BSE isolate to assess their relative susceptibility to BSE infection. Goats were killed at different time points during the incubation period and after the onset of clinical signs, and their brains as well as several peripheral tissues were analyzed for the accumulation of pathological prion protein (PrPSc) and prion infectivity by mouse bioassay.
Results. R/Q211 goats displayed delayed clinical signs compared with wild-type goats. Deposits of PrPSc were detected only in brain, whereas infectivity was present in peripheral tissues too. In contrast, none of the Q/K222 goats showed any evidence of clinical prion disease. No PrPSc accumulation was observed in their brains or peripheral tissues, but very low infectivity was detected in some tissues very long after inoculation (44–45 months).
Conclusions. These results demonstrate that transmission of goat BSE is genotype dependent, and they highlight the pivotal protective effect of the K222 PRNP variant in the oral susceptibility of goats to BSE.
Role of the Goat K222-PrPC Polymorphic variant in Prion Infection Resistance
Aguilar-Calvo, P. ; Espinosa, J.C. ; Pintado, B. ; Gutiérrez-Adán, A. ; Alamilo, E. ; Miranda, A. ; Prieto, I. ; Bossers, A. ; Andreoletti, O. ; Torres, J.M. - \ 2014
Journal of Virology 88 (2014)5. - ISSN 0022-538X - p. 2670 - 2676.
bovine spongiform encephalopathy - protein gene polymorphisms - caprine prp gene - natural scrapie - classical scrapie - transgenic mice - sheep - identification - association - genotype
The prion protein-encoding gene (prnp) strongly influences the susceptibility of small ruminants to transmissible spongiform encephalopathies (TSEs). Hence, selective breeding programs have been implemented to increase sheep resistance to scrapie. For goats, epidemiological and experimental studies have provided some association between certain polymorphisms of the cellular prion protein (PrPC) and resistance to TSEs. Among them, the Q/K polymorphism at PrPC codon 222 (Q/K222) yielded the most promising results. In this work, we investigated the individual effects of the K222-PrPC variant on the resistance/susceptibility of goats to TSEs. For that purpose, we generated two transgenic mouse lines, expressing either the Q222 (wild type) or K222 variant of goat PrPC. Both mouse lines were challenged intracerebrally with a panel of TSE isolates. Transgenic mice expressing the wild-type (Q222) allele were fully susceptible to infection with all tested isolates, whereas transgenic mice expressing similar levels of the K222 allele were resistant to all goat scrapie and cattle BSE isolates but not to goat BSE isolates. Finally, heterozygous K/Q222 mice displayed a reduced susceptibility to the tested panel of scrapie isolates. These results demonstrate a highly protective effect of the K222 variant against a broad panel of different prion isolates and further reinforce the argument supporting the use of this variant in breeding programs to control TSEs in goat herds. IMPORTANCE The objective of this study was to determine the role of the K222 variant of the prion protein (PrP) in the susceptibility/resistance of goats to transmissible spongiform encephalopathies (TSEs). Results showed that transgenic mice expressing the goat K222-PrP polymorphic variant are resistant to scrapie and bovine spongiform encephalopathy (BSE) agents. This protective effect was also observed in heterozygous Q/K222 animals. Therefore, the single amino acid exchange from Q to K at codon 222 of the cellular prion protein provides resistance against TSEs. All the results presented here support the view that the K222 polymorphic variant is a good candidate for selective breeding programs to control and eradicate scrapie in goat herds.