Prion diseases are associated with the conversion of the ␣-helix rich prion protein (PrP C ) into a ␤-structure-rich insoluble conformer (PrP Sc ) that is thought to be infectious. The mechanism for the PrP C 3 PrP Sc conversion and its relationship with the pathological effects of prion diseases are poorly understood, partly because of our limited knowledge of the structure of PrP Sc . In particular, the way in which mutations in the PRNP gene yield variants that confer different susceptibilities to disease needs to be clarified. We report here the 2.5-Å-resolution crystal structures of three scrapie-susceptibility ovine PrP variants complexed with an antibody that binds to PrP C and to PrP Sc ; they identify two important features of the PrP C 3 PrP Sc conversion. First, the epitope of the antibody mainly consists of the last two turns of ovine PrP second ␣-helix. We show that this is a structural invariant in the PrP C 3 PrP Sc conversion; taken together with biochemical data, this leads to a model of the conformational change in which the two PrP C Cterminal ␣-helices are conserved in PrP Sc , whereas secondary structure changes are located in the N-terminal ␣-helix. Second, comparison of the structures of scrapie-sensitivity variants defines local changes in distant parts of the protein that account for the observed differences of PrP C stability, resistant variants being destabilized compared with sensitive ones. Additive contributions of these sensitivity-modulating mutations to resistance suggest a possible causal relationship between scrapie resistance and lowered stability of the PrP protein.

This study reports the first evidence of circulation of avian influenza viruses (AIV) in domestic poultry in Mali. In the Mopti region, where AIV have already been isolated in migratory water birds, we sampled 223 backyard domestic birds potentially in contact with wild birds and found that 3.6% had tracheal or cloacal swabs positive by real-time reverse transcription PCR (rRT-PCR) for type A influenza viruses (IVA) and that 13.7% had sera positive by commercial ELISA test detecting antibodies against IVA. None of the birds positive by rRT-PCR for IVA was positive by rRT-PCR for H5 and H7 subtypes, and none showed any clinical signs therefore indicating the circulation of low pathogenic avian influenza. Unfortunately, no virus isolation was possible. Further studies are needed to assess the temporal evolution of AIV circulation in the Mopti region and its possible correlation with the presence of wild birds.

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