Intraspecies Transmission of BASE Induces Clinical Dullness and Amyotrophic Changes

Guerino Lombardi,Sergio Ferrari,Cristiano Corona,Barbara Iulini,Lorenzo Capucci,Michele Fiorini,Fabrizio Tagliavini,Maria Caramelli,Cristina Casalone,Gianluigi Zanusso,Daniela Gelmetti,Elisa Fasoli,Ilaria Barbieri,Alessia Farinazzo,Matteo Gelati,Salvatore Monaco,Antonio D' Angelo,Gloria Torcoli,David Westaway

doi:10.1371/journal.ppat.1000075

Abstract

The disease phenotype of bovine spongiform encephalopathy (BSE) and the molecular/ biological properties of its prion strain, including the host range and the characteristics of BSE-related disorders, have been extensively studied since its discovery in 1986. In recent years, systematic testing of the brains of cattle coming to slaughter resulted in the identification of at least two atypical forms of BSE. These emerging disorders are characterized by novel conformers of the bovine pathological prion protein (PrPTSE), named high-type (BSE-H) and low-type (BSE-L). We recently reported two Italian atypical cases with a PrPTSE type identical to BSE-L, pathologically characterized by PrP amyloid plaques and known as bovine amyloidotic spongiform encephalopathy (BASE). Several lines of evidence suggest that BASE is highly virulent and easily transmissible to a wide host range. Experimental transmission to transgenic mice overexpressing bovine PrP (Tgbov XV) suggested that BASE is caused by a prion strain distinct from the BSE isolate. In the present study, we experimentally infected Friesian and Alpine brown cattle with Italian BSE and BASE isolates via the intracerebral route. BASE-infected cattle developed amyotrophic changes accompanied by mental dullness. The molecular and neuropathological profiles, including PrP deposition pattern, closely matched those observed in the original cases. This study provides clear evidence of BASE as a distinct prion isolate and discloses a novel disease phenotype in cattle.

Highlights

Transmissible spongiform encephalopathies (TSEs), are mammalian neurodegenerative disorders of sporadic, genetic, or infectious origin characterized by accumulation and deposition of an abnormal isoform (PrPTSE) of the cellular prion protein (PrPC) in the brain [1]
In bovine amyloidotic spongiform encephalopathy (BASE)-treated cattle the clinical disease duration was shorter than in bovine spongiform encephalopathy (BSE)-inoculated animals; caution in evaluating these differences is dictated by the low number of experimental animals in addition to the undetermined infectivity titre of the inocula
We demonstrate that BSE and BASE isolates maintain distinct biological properties and induce different disease phenotypes after transmission in their natural host

Summary

Introduction

Transmissible spongiform encephalopathies (TSEs), are mammalian neurodegenerative disorders of sporadic, genetic, or infectious origin characterized by accumulation and deposition of an abnormal isoform (PrPTSE) of the cellular prion protein (PrPC) in the brain [1]. TSEs include a wide range of animal and human disorders, such as BSE in cattle, scrapie in sheep and goats, chronic wasting disease in deer and elk, and Creutzfeldt-Jakob disease (CJD) in humans [1]. First identified in 1986 in the UK, BSE has been confirmed in over 180,000 cases, more than one million cattle have been estimated to be infected [2]. Evidence of the spread of the BSE agent across certain mammalian species, including humans, indicates that this disease is a major animal and human public health issue [3,4,5]. Progression to behavioural, sensory and posture/movement alterations led to death within a few months [6,7]

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