Please cite this article in press as: Aguilar-Calvo, P., et al., Prion and prion-like diseases in animals. Virus Res. (2014), http://dx.doi.org/10.1016/j.virusres.2014.11.026 ARTICLE IN PRESS G Model VIRUS-96466; No. of Pages 12 Virus Research xxx (2014) xxx–xxx Contents lists available at ScienceDirect Virus Research j ourna l h o mepa ge: www.elsevier.com/locate/virusres Prion and prion-like diseases in animals Patricia Aguilar-Calvo a , Consolación García a , Juan Carlos Espinosa a , Olivier Andreoletti b , Juan María Torres a,* a Centro de Investigación en Sanidad Animal (CISA-INIA), 28130 Valdeolmos, Madrid, Spain b INRA, UMR 1225, Interactions Hôtes Agents Pathogènes, École Nationale Vétérinaire de Toulouse, 23 chemin des Capelles, 31076 Toulouse Cedex, France a r t i c l e i n f o Article history: Available online xxx Keywords: Prion Amyloid Amyloidosis Protein misfolding Protein self-templating Prion-like transmission a b s t r a c t Transmissible spongiform encephalopaties (TSEs) are fatal neurodegenerative diseases characterized by the aggregation and accumulation of the misfolded prion protein in the brain. Other proteins such as -amyloid, tau or Serum Amyloid-A (SAA) seem to share with prions some aspects of their pathogenic mechanism; causing a variety of so called prion-like diseases in humans and/or animals such as Alzheimer’s, Parkinson’s, Huntington’s, Type II diabetes mellitus or amyloidosis. The question remains whether these misfolding proteins have the ability to self-propagate and transmit in a similar manner to prions. In this review, we describe the prion and prion-like diseases affecting animals as well as the recent findings suggesting the prion-like transmissibility of certain non-prion proteins. © 2014 Elsevier B.V. All rights reserved. 1. Introduction Prion diseases or Transmissible Spongiform Encephalopaties (TSEs) are fatal neurodegenerative diseases that affect a diver- sity of mammal species including Creutzfeldt–Jacob disease (CJD), kuru, Gerstmann-Sträussler-Scheinker disease (GSS), and famil- ial fatal insomnia (FFI) in humans, as well as scrapie in sheep and goats, bovine spongiform encephalopathy (BSE) in cattle, and chronic wasting disease (CWD) in deer and elk. Prion dis- eases are characterized by long incubation times (from months to decades), development of neuropathological alterations and symptoms primarily neurological including behavior abnormali- ties, motor dysfunction, cognitive impairment and cerebral ataxia. Prion diseases do not produce immune response and nowadays no effective therapies are available for their treatment. Prion diseases are caused by the conversion of the physio- logical cellular prion protein (PrP C ) into a pathogenic -sheets enriched isoform designated PrP Sc , which is able to self-propagate by recruiting PrP C . This conformational change confers PrP Sc with an increased tendency to aggregate, insolubility in non-ionic deter- gents, high resistance to heat and chemical sterilization, and partial resistance to protease digestion. The concept of proteinaceous infectious particles, “Prions”, was first recapitulated in the “Prion Protein Only Hypothesis” (Prusiner, 1982). To date, a number of studies have supported this contention, including the successful * Corresponding author. Tel.: +34 91 620 23 00; fax: +34 91 620 22 47. E-mail address: jmtorres@inia.es (J.M. Torres). induction of neurodegenerative diseases just from recombinant amyloid forms of prions (Castilla et al., 2005; Colby et al., 2009; Legname et al., 2004) or in combination with certain lipids and RNA factors (Wang et al., 2010). Nevertheless, some findings suggest that the misfolded PrP Sc protein alone is not necessarily infectious by itself and needs some cofactors to self-propagate (Deleault et al., 2012; Saa et al., 2012; Telling et al., 1995). Hence, some authors pro- posed that PrP Sc formation and infectious agent replication might constitute two separated processes where infectivity could lay on other non-PrP structures (reviewed in Manuelidis, 2013). Despite these arguments, prion diseases are entirely dependent on the expression of endogenous PrP C , as confirmed by the total resistance of prnp knock-out mice to prion infection (Bueler et al., 1993; Prusiner et al., 1993). PrP C is a glycosylphosphatidylinosi- tol (GPI)-anchored plasma membrane protein encoded by the prnp gene which is well conserved throughout evolution in mammals (Nicolas et al., 2009). PrP C is mostly expressed in central nervous system (CNS) but also in the lymphoreticular system (LRS), skeletal muscle, heart, kidney, digestive tract, skin, blood plasma, mammary gland and endothelia (Nuvolone et al., 2009). Despite its ubiqui- tous expression and distribution, its physiological function is not yet clear. The mechanism by which PrP C converts into PrP Sc adopting the capacity to self-template is neither well-known. PrP C can fold into a variety of thermodynamically stable PrP Sc conformers (Prusiner, 1998; Wiltzius et al., 2009) whose mixture in a relative propor- tion may result in different prion strains (Angers et al., 2010). Each prion strain displays a specific disease phenotype (includ- ing incubation times, clinical signs, and histopathological lesions http://dx.doi.org/10.1016/j.virusres.2014.11.026 0168-1702/© 2014 Elsevier B.V. All rights reserved.