MedicalResearch.com Interview with:
Romolo Nonno, DVM, PhD
Istituto Superiore di Sanità
Dipartimento di Sanità Pubblica Veterinaria e Sicurezza Alimentare
Roma Italy
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: Previous studies have suggested that prion populations are composed of a variety of conformational variants subjected to Darwinian evolution driven by selective regimes. However, the exact molecular mechanisms that make prions able to self-replicate and mutate are still poorly understood.
A major technical advance in this field has been the discovery of techniques that allow to replicate prions in vitro, outside live organisms. One of these techniques, Protein Misfolding Cyclic Amplification (PMCA), allows to grow prion populations for a very high number of replications in a relatively short time period.
Furthermore it is conceivable that the in vitro environment offers less constraint to prion replication than live animals or cells, due to the absence of active clearance and cell division, which are key players of conformers selection in ex vivo models. These features make PMCA an attractive tool to investigate prion replication, mutation and evolution. By using PMCA, we investigated the in vitro evolution of prion populations derived from natural scrapie. Unexpectedly, we found that the cloud of conformational variants which compose a natural scrapie isolate also includes “defective” variants which, once isolated, are unable to self-sustain in vivo.
Importantly, we found that the defective prion mutant that we have isolated possesses unique biochemical properties in that its prion domain lacks the central region of prion protein, which is invariably present in known infectious mammalian prions.
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