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L-type Bovine Prions in Peripheral Nerve Tissues | CDC EID

EID Journal Home > Volume 16, Number 7–July 2010

Volume 16, Number 7–July 2010
Accumulation of L-type Bovine Prions in Peripheral Nerve Tissues
Yoshifumi Iwamaru, Morikazu Imamura, Yuichi Matsuura, Kentaro Masujin, Yoshihisa Shimizu, Yujing Shu, Megumi Kurachi, Kazuo Kasai, Yuichi Murayama, Shigeo Fukuda, Sadao Onoe, Ken'ichi Hagiwara, Yoshio Yamakawa, Tetsutaro Sata, Shirou Mohri, Hiroyuki Okada, and Takashi Yokoyama
Author affiliations: National Institute of Animal Health, Tsukuba, Ibaraki, Japan (Y. Iwamaru, M. Imamura, Y. Matsuura, K. Masujin, Y. Shimizu, Y. Shu, M. Kurachi, K. Kasai, Y. Murayama, S. Mohri, H. Okada, T. Yokoyama); Hokkaido Animal Research Center, Hokkaido, Japan (S. Fukuda, S. Onoe); and National Institute of Infectious Diseases, Tokyo, Japan (K. Hagiwara, Y. Yamakawa, T. Sata)

Suggested citation for this article

We recently reported the intraspecies transmission of L-type atypical bovine spongiform encephalopathy (BSE). To clarify the peripheral pathogenesis of L-type BSE, we studied prion distribution in nerve and lymphoid tissues obtained from experimentally challenged cattle. As with classical BSE prions, L-type BSE prions accumulated in central and peripheral nerve tissues.
Bovine spongiform encephalopathy (BSE) is a fatal neurodegenerative disorder of cattle characterized by accumulation of a protease-resistant form of a normal cellular prion protein (PrPres) in the central nervous system. The scientific literature in general has assumed that BSE in cattle is caused by a uniform strain (classical BSE). However, different neuropathologic and molecular phenotypes of BSE (atypical BSEs) have recently been reported from various countries (1). Recent data from Western blot analyses of field cases of atypical BSEs are characterized by a higher (H-type BSE) or lower (L-type BSE) molecular mass of the unglycosylated form of PrPres than is classical BSE (2). The origins of atypical BSEs remain obscure; unlike classical BSE, atypical BSE has been detected mainly in aged cattle and suggested a as possible sporadic form of BSE (3).

Several lines of evidence demonstrate that classical BSE and a variant form of Creutzfeldt-Jacob disease are most likely caused by the same agent (4,5). Transmission of classical BSE to humans has been proposed to result from ingestion of contaminated food. Whether atypical BSEs are transmissible to humans remains uncertain; however, human susceptibility to L-type BSEs is suggested by recent experimental transmission in primates (6) and mice transgenic for human prion protein (PrP) (7) by using the most effective route of intracerebral inoculations of prions. The L-type BSE prion is much more virulent in primates and in humanized mice than is the classical BSE prion, which suggests the possibility of zoonotic risk associated with the L-type BSE prion. These findings emphasize the critical importance of understanding tissue distribution of L-type BSE prions in cattle because, among the current administrative measures for BSE controls, the specified risk materials removal policy plays a crucial role in consumer protection.

In Japan, atypical BSE was detected in an aged Japanese Black cow (BSE/JP24) (8). We recently reported the successful transmission of BSE/JP24 prions to cattle and showed that the characteristics of these prions closely resemble those of L-type BSE prions found in Italy (9). In this study, we report the peripheral distribution of L-type BSE prions in experimentally challenged cattle.

The Study
The Animal Ethics Committee and Animal Care and Use Committee of the National Institute of Animal Health approved the study. Five Holstein calves 2–3 months of age were intracerebrally injected with 1 mL of 10% (w/v) brain homogenates prepared from the medulla oblongata of BSE/JP24. In our earlier report, experimentally challenged cattle appeared to display clinical signs indicative of BSE at 11 months postinoculation (mpi) (9). Animals were sequentially euthanized before and after the onset of clinical signs (cattle identification codes 8515 and 496 at 10 and 12 mpi, respectively) and at the terminal stage of the disease (cattle identification codes 528, 1061, and 5566 at 16 mpi). A wide range of tissues was sampled at subsequent necropsy. We provisionally categorized the adrenal gland as nerve tissue because of the presence of chromaffin cells in the medulla of the gland.

Western blot analysis for PrPres was performed on obex tissue samples as described previously by using anti-PrP monoclonal antibody T2 (9). PrPres was detectable in all obex samples obtained 10, 12, and 16 mpi, suggesting that transmission of L-type BSE prions to these animals was successful. Dilution of the protease-treated brain sample and analysis of Western blot results showed that the detection threshold for PrPres was 1.25 μg of brain tissue equivalent (data not shown).

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L-type Bovine Prions in Peripheral Nerve Tissues | CDC EID

Suggested Citation for this Article
Imamura YIM, Matsuura Y, Masujin K, Shimizu Y, Shu Y, Kurachi M, et al. Accumulation of L-type bovine prions in peripheral nerve tissues. Emerg Infect Dis [serial on the Internet]. 2010 Jul [date cited].

DOI: 10.3201/eid1607.091882

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