Extraneural prion neuroinvasion without lymphoreticular system infection

Area of Science:

• Veterinary Neurology
• Infectious Diseases
• Prion Biology

Background:

• Prion diseases, like bovine spongiform encephalopathy, challenge the necessity of lymphoreticular system (LRS) infection for neuroinvasion.
• Investigating alternative neuroinvasion routes is crucial for understanding prion pathogenesis.

Purpose of the Study:

• To determine the role of LRS prion infection in neuroinvasion following extraneural inoculation.
• To investigate the neuroinvasive potential of transmissible mink encephalopathy (TME) agent strains (HY and DY) via different routes.

Main Methods:

• Extraneural inoculation (intraperitoneal, oral, intratongue) of HY and DY TME agents in hamsters.
• Monitoring for clinical signs of disease.
• Detection of prion infectivity and PrP(Sc) in lymphoid tissues (spleen, lymph nodes) and neural tissues (brainstem, brain).

Main Results:

• DY TME agent did not replicate in LRS tissues or cause disease after peripheral inoculation.
• HY TME agent replicated in LRS tissues and induced disease following peripheral inoculation.
• Intratongue inoculation with DY TME agent led to prion disease and detection in the tongue and brainstem, without LRS involvement.

Conclusions:

• Neuroinvasion by the DY TME agent can occur from the tongue to the brain via cranial nerves, independent of LRS infection.
• These findings support prion neuroinvasion from peripheral, highly innervated tissues without LRS replication in livestock prion diseases.