Generation of a persistently infected MDBK cell line with natural bovine spongiform encephalopathy (BSE)

Area of Science:

• Veterinary Neurology
• Molecular Biology
• Infectious Diseases

Background:

• Bovine Spongiform Encephalopathy (BSE) is a zoonotic prion disease with implications for human health (variant Creutzfeldt-Jakob disease).
• Current research lacks in vitro models for studying BSE, specifically the replication of proteinase K-resistant BSE (PrPBSE).

Purpose of the Study:

• To establish a cell culture model for the in vitro replication of the BSE agent.
• To facilitate the study of potential therapeutic agents and diagnostic methods for BSE.

Main Methods:

• Generation of a Madin-Darby Bovine Kidney (MDBK) cell line over-expressing the bovine prion protein.
• Infection of the engineered cell line with naturally BSE-infected bovine brain homogenate.
• Monitoring of PrPBSE replication and accumulation over multiple passages.

Main Results:

• The engineered MDBK cell line successfully replicated and accumulated PrPBSE after exposure to BSE-infected brain homogenate.
• The infection was maintained in the cell line up to passage 83.
• This marks the first demonstration of BSE agent infection in cell lines over-expressing the bovine prion protein.

Conclusions:

• A novel BSE-infected cell line has been established, overcoming previous limitations in prion disease research.
• This cell line serves as a valuable tool for in vitro studies of BSE pathogenesis and the evaluation of therapeutic strategies.
• The findings contribute to a better understanding of prion diseases and their potential zoonotic transmission.