Abstract
The amyloidotic form of bovine spongiform encephalopathy (BSE) termed BASE is caused by a prion strain whose biological properties differ from those of typical BSE, resulting in a clinically and pathologically distinct phenotype. Whether peripheral tissues of BASE-affected cattle contain infectivity is unknown. This is a critical issue since the BASE prion is readily transmissible to a variety of hosts including primates, suggesting that humans may be susceptible. We carried out bioassays in transgenic mice overexpressing bovine PrP (Tgbov XV) and found infectivity in a variety of skeletal muscles from cattle with natural and experimental BASE. Noteworthy, all BASE muscles used for inoculation transmitted disease, although the attack rate differed between experimental and natural cases (∼70% versus ∼10%, respectively). This difference was likely related to different prion titers, possibly due to different stages of disease in the two conditions, i.e. terminal stage in experimental BASE and pre-symptomatic stage in natural BASE. The neuropathological phenotype and PrPres type were consistent in all affected mice and matched those of Tgbov XV mice infected with brain homogenate from natural BASE. The immunohistochemical analysis of skeletal muscles from cattle with natural and experimental BASE showed the presence of abnormal prion protein deposits within muscle fibers. Conversely, Tgbov XV mice challenged with lymphoid tissue and kidney from natural and experimental BASE did not develop disease. The novel information on the neuromuscular tropism of the BASE strain, efficiently overcoming species barriers, underlines the relevance of maintaining an active surveillance.
Highlights
In 2004 an atypical form of bovine spongiform encephalopathy (BSE) termed BASE or BSE-L was identified in Italy through active surveillance [1] and subsequently recognized in different European countries, North America, Canada and Japan [1,2,3,4,5,6]
Groups of mice were inoculated with brain homogenates from the same experimentally BASE-infected cattle and from a natural BASE identified by active surveillance (#12966/07)
No PrPSc type distinguished by a protease-resistant core (PrPres) was detected in muscle homogenate used for inoculation by immunoblot analysis without or with PrPres enrichment with phosphotungstic acid (PTA) precipitation [16]
Summary
In 2004 an atypical form of bovine spongiform encephalopathy (BSE) termed BASE or BSE-L was identified in Italy through active surveillance [1] and subsequently recognized in different European countries, North America, Canada and Japan [1,2,3,4,5,6]. Tg mice overexpressing human PrP as well as non-human primates are more susceptible to infection with BASE than with BSE [11,12,13,14] Overall these data raise concern about the potential risk of transmission of BASE to humans and it is urgent to determine the presence and distribution of infectivity in peripheral tissues of BASE-affected cattle. To investigate this issue, we inoculated Tgbov mice with different peripheral tissues from experimentally and naturally BASE-affected cattle and found that various skeletal muscles contained infectivity and PrP-immunoreactive deposits within individual fibers
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