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Infectology

Introduction

The Scripps Research Institute's Department of Infectology, the first department to be established on the Florida campus, in 2004, focuses on prion diseases and hepatitis C. Prions are infectious agents that consist of protein and are devoid of a nucleic acid-based genome. They cause invariably lethal diseases of the central nervous system, such as mad cow disease, once rampant in the UK, chronic wasting disease of mule deer and elk in the US, or Creutzfeldt-Jakob disease in humans. The Department has established a novel, rapid cell-based assay for prions that has been extended to allow discrimination between different prion strains. It studies the properties of prions, the mechanisms of their propagation and the molecular basis of strains both in cell culture and in cell-free systems. Assays for high-throughput screening of potential anti-prion drugs are under development. The other pathogen under investigation is hepatitis C virus. Basic research addresses the mechanism of replication of the virus, with a view to identifying new approaches to inhibit viral replication. One approach, aimed at disrupting the formation of infectious virus particles, has provided interesting lead compounds that are currently being explored. A second approach, based on the structural analysis of viral proteins, focuses on inhibiting the replication of the viral RNA and is aimed at developing novel drugs. Much of our past effort has been dedicated to understand the pathogenesis and the mechanisms of prion transmission from one species to another and its propagation within the body. We also studied the neurotoxic mechanisms and showed, using primary cultures of neurons, that low molecular weight aggregates of the prion protein are neurotoxic. In collaborative studies, we have found that the non integrin laminin receptor can act as a cellular receptor for the prion protein. Our aim now is to devise intervention strategies based on the blockage of the neurotoxic entities on the one hand, and of prion replication on the other hand, using a two step approach in scrapie-infected cells and rodent models of prion diseases.