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

## TL;DR

This study shows that L-type BSE prions retain their key traits after being transmitted within cynomolgus monkeys, supporting their zoonotic potential and stable pathogenesis.

## Contribution

Demonstrates the stability of L-BSE prion strain traits after intraspecies transmission in nonhuman primates.

## Key findings

- L-BSE prions caused disease in monkeys with similar endpoints and brain pathology as in primary transmission.
- L-BSE prions remained non-transmissible to mice after monkey passage, unlike C-BSE prions.
- Prion traits such as vacuolation and PrPSc distribution were consistent across transmission rounds.

## Abstract

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 (PrPSc) in the cerebrum, and sparse PrPSc 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.