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Mammalian prions, transmissible agents causing lethal neurodegenerative diseases, are composed of assemblies of misfolded cellular prion protein (PrP). A novel PrP variant, G127V, was under positive evolutionary selection during the epidemic of kuru--an acquired prion disease epidemic of the Fore population in Papua New Guinea--and appeared to provide strong protection against disease in the heterozygous state. Here we have investigated the protective role of this variant and its interaction with the common, worldwide M129V PrP polymorphism. V127 was seen exclusively on a M129 PRNP allele. We demonstrate that transgenic mice expressing both variant and wild-type human PrP are completely resistant to both kuru and classical Creutzfeldt-Jakob disease (CJD) prions (which are closely similar) but can be infected with variant CJD prions, a human prion strain resulting from exposure to bovine spongiform encephalopathy prions to which the Fore were not exposed. Notably, mice expressing only PrP V127 were completely resistant to all prion strains, demonstrating a different molecular mechanism to M129V, which provides its relative protection against classical CJD and kuru in the heterozygous state. Indeed, this single amino acid substitution (G→V) at a residue invariant in vertebrate evolution is as protective as deletion of the protein. Further study in transgenic mice expressing different ratios of variant and wild-type PrP indicates that not only is PrP V127 completely refractory to prion conversion but acts as a potent dose-dependent inhibitor of wild-type prion propagation.

Background: In March 1996, revelations about the possible risk for humans of the 'mad cow disease' epidemic had a sudden impact on the diets of European populations., Objective: To assess changes in meat and nutrient intakes in adults living in Geneva, Switzerland from 1993 to 2000., Design: Independent annual cross-sectional surveys (4047 women and 4092 men total)., Main Outcome Measure: Dietary habits assessed and compared to baseline (January 1993-April 1996) via validated semi-quantitative food-frequency questionnaire., Results: Women beef abstainers increased from 8.9 to 14.9% in late 1996 (P<0.001) and 13.3% in 1997 (P<0.05); among meat consumers, in late 1996 meat/beef intakes declined -10/-12% (both P<0.05). From 1997 to 2000 most intake levels drifted back toward those at baseline, but chicken intakes were significantly (all P<0.05) greater each year (+19% in 2000 (P<0.001). Consistent but less dramatic changes were observed among men. From late 1996 until 2000, liver abstention was significantly (all P<0.05) greater (women from 60 to 78%; men from 61 to 73% in 2000; (both P<0.001). The only nutrient intakes that decreased significantly (all P<0.05) each year from 1997 through 2000 were retinol and total vitamin A women: -22% (P<0.001); -11% (P<0.05) respectively; men: -16% (P<0.001); -10% (P<0.05) respectively, in 2000). Total vitamin A intakes exceeded the dietary reference intake (DRI) for liver eaters (women 185%, men 153%), but were below the DRI for liver abstainers (women 83%; men 66%) in 2000., Conclusion: The decreases in beef and liver consumption since late 1996 led to the discovery of a long-term disparity in the retinol and total vitamin A intakes of liver eaters vs abstainers.

Objective: To assess differences in dietary habits in the general population of Geneva, Switzerland, after the 1996 (BSE) crisis., Design: Repeated population-based survey during 1993, 1994, 1995 and 1996., Setting: The Bus Santé 2000 epidemiological observatory of Geneva, Switzerland., Subjects: A representative sample of 1190 men and 1154 women., Main Outcome Measure: Dietary habits assessed by a semi-quantitative food frequency questionnaire., Results: The proportion of women who reported not having eaten beef was 7.7% in 1993-1995 and went up to 14.6% in 1996 (age-adjusted difference +6.4%, 95% CI +2.4 to +10.4). Among men, the proportion of non-beef-eaters remained constant (5%). There was a sharp increase of women who did not eat liver (+14.7%, +9.1 to +20.3) but less so in men (+2 5.1%, -0.7 to +10.8). Among women who ate meat, the amount of beef intake decreased by 120 g/month (95% CI -208 to -36). While chicken intake increased (+44 g/month, -2 to 88), overall intake of meat (including poultry but not fish) declined by 204 g/month (or 2.7 kg per year). In men the decrease in beef intake was not statistically significant (-48 g/month, -172 to 80), but consumption of chicken increased (+2 56g/month, +8 to +104). Fish intake was stable in both genders. The reduction in intake of animal protein (-3.5 g/day) in women and of retinol intake in both sexes (women -77 micrograms/day; men -56 micrograms/day) was statistically significant., Conclusions: The BSE crisis coincided with spontaneous differences in food habits, especially in women, that may have nutritional consequences at the population level.