Strain Traits of Intracranially Administered L‐Type Bovine Spongiform Encephalopathy Prions Are not Significantly Modified During Intraspecies Transmission in Cynomolgus Monkeys                    

Ken'ichi Hagiwara, Hiroaki Shibata, Minoru Tobiume, Yuko Sato, Keiko Ohto, Sachi Okabayashi, Nozomi Nakano, Motohiro Horiuchi, Fumiko Ono

Among the three prion strains of bovine spongiform encephalopathy (BSE), classical BSE (C‐BSE) prions are known causative agents of variant Creutzfeldt–Jakob disease. By contrast, human infections with L‐type (L‐) or H‐type (H‐) BSE prions have not been reported. Nonetheless, the zoonotic potential of L‐BSE prions is supported by their successful primary transmission from cattle to cynomolgus macaque ( Macaca fascicularis ) monkeys via intracranial challenge. To assess whether the defining strain traits of L‐BSE prions remain stable following secondary intraspecies transmission, we prepared brain homogenates from a diseased macaque that had previously undergone primary transmission of L‐BSE prions, and intracranially administered them into two naïve macaques. Both animals succumbed to the disease within humane endpoints comparable to those observed in the primary transmission. Histopathological and immunohistochemical analyses of brain tissues showed no significant changes relative to primary transmission, including severe vacuolation and fine synaptic distribution of disease‐associated forms of prion protein (PrP Sc ) in the cerebrum, and sparse PrP Sc plaques in the cerebellum. In bioassays using C57BL/6 J mice, cattle‐derived L‐BSE prions and those passaged once or twice in macaques failed to transmit to mice, whereas cattle‐derived C‐BSE prions and their macaque‐passaged counterparts were transmissible. These findings refine our understanding of L‐BSE pathogenesis and confirm the stability of L‐BSE prions following intracranial transmission in a nonhuman primate model.

Microbiology and Immunology

Wiley

第70巻

第3号

166

174

0385-5600

10.1111/1348-0421.70040