JVI Accepts, published online ahead of print on 30 January 2008

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J. Virol. doi:10.1128/JVI.02561-07
Copyright (c) 2008, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

Evaluation of the Human Transmission Risk of an Atypical Bovine Spongiform Encephalopathy Prion Strain

Qingzhong Kong^*, Mengjie Zheng, Cristina Casalone, Liuting Qing, Shenghai Huang, Bikram Chakraborty, Ping Wang, Fusong Chen, Ignazio Cali, Cristiano Corona, Francesca Martucci, Barbara Iulini, Pierluigi Acutis, Lan Wang, Jingjing Liang, Meiling Wang, Xinyi Li, Salvatore Monaco, Gianluigi Zanusso, Wen-Quan Zou, Maria Caramelli, and Pierluigi Gambetti^*

Department of Pathology, Case Western Reserve University, Cleveland, OH 44106, USA; CEA, Istituto Zooprofilattico Sperimentale, 10154 Torino, Italy; Department of Neurological and Visual Sciences, University of Verona, 37134 Verona, Italy

^* To whom correspondence should be addressed. Email: qxk2{at}case.edu. pxg13{at}case.edu.

Bovine spongiform encephalopathy (BSE), the prion disease in cattle, was widely believed to have only one strain (BSE-C). BSE-C causes the fatal prion disease named new variant Creutzfeldt-Jacob disease in humans. Two atypical BSE strains, BASE (or BSE-L) and BSE-H, have been discovered in several countries since 2004; their transmissibility and phenotypes in humans are unknown. We investigated the infectivity and human phenotype of BASE by inoculating transgenic (Tg) mice expressing the human prion protein with brain homogenates from two BASE-affected cattle. Sixty percent of the inoculated Tg mice became infected after 20-22 months incubation, a transmission rate higher than those reported for BSE-C. A quarter of BASE-infected Tg mice, but none of the Tg mice infected with a sporadic human prion disease, showed presence of pathogenic prion protein isoforms in the spleen, indicating that the BASE prion is intrinsically lymphotropic. The pathological prion protein isoforms in BASE-infected humanized Tg mouse brains are different from those of the original cattle BASE or sporadic human prion disease. Minimal brain spongiosis and long incubation time are observed in the BASE-infected Tg mice. These results suggest that, in humans, BASE is a more virulent BSE strain and likely lymphotropic.