Lack of Evidence for Transmission of Atypical H‐Type Bovine Spongiform Encephalopathy Prions (H‐BSE Prions) by Intracranial and Oral Challenges to Nonhuman Primates

ABSTRACT Bovine spongiform encephalopathy (BSE) is a prion disease in cattle caused by classical‐type (C‐), L‐type (L‐), or H‐type (H‐) BSE prions. While C‐BSE prions are zoonotic agents responsible for variant Creutzfeldt–Jakob disease, L‐ and H‐BSE prions are believed not to be connected to human prion diseases. However, L‐BSE prions have been shown to transmit to cynomolgus monkeys (Macaca fascicularis), suggesting they may have zoonotic potential. In the present study, we examined whether H‐BSE prions are transmissible to cynomolgus monkeys. The monkeys were injected intracranially (n = 2) or given orally (n = 2) with brain homogenates from a cow infected with H‐BSE prions. After asymptomatic observation periods of 4–6 years, the monkeys were euthanized for autopsy. Histological examination of the brain did not reveal any pathological changes. Immunohistochemical and Western blot analyses did not detect disease‐associated forms of prion protein (PrPSc) in the brain, peripheral neurons, or lymphatic tissues. The unsuccessful transmission indicates an effective barrier against the transmission of cattle H‐BSE prions to cynomolgus monkeys. Based on the results obtained in this nonhuman primate model, we estimated that the potential transmission of H‐BSE prions to humans is substantially lower than C‐ and L‐BSE prions.