18Prions- VMicro101

Introduction to Prions

  • Prions are infectious proteinaceous particles responsible for certain neurodegenerative diseases.

  • Prions lack nucleic acids, unlike viruses and other infectious agents.

  • They are associated with several diseases affecting both humans and animals.

Slow-Progressing Diseases

  • Classic diseases are slow-progressing disorders that typically culminate in death.

  • These diseases are driven by transmissible agents known as prions, not directly neurotoxic.

  • Misfolded soluble intermediates and amyloid-like fibril deposits may exert toxic effects through various mechanisms.

  • Examples of slow virus diseases include:

    • Kuru

    • Creutzfeldt-Jakob disease in humans

    • Scrapie

    • Transmissible mink encephalopathy (TME) in animals.

Characteristics of Prions

  • Prions are infectious protein particles responsible for a group of diseases known as transmissible spongiform encephalopathies (TSEs).

  • Unique features:

    • Composed solely of protein, devoid of nucleic acid.

    • Non-immunogenic and extremely resistant to various inactivation methods (heat, chemicals, irradiation).

Prion Theory

  • Two main types of prions exist: those associated with mammals and those associated with fungi.

  • The prion theory suggests that prions arise from normal glycoproteins that undergo pathological changes leading to TSEs.

  • Bovine spongiform encephalopathy (BSE) strain is notably promiscuous, affecting various species.

Mechanisms of Conversion

  • PrPC (normal form) can convert to PrPSc (abnormal form) through:

    1. Spontaneous conversion of PrPC to PrPSc.

    2. Interaction with ingested/injected PrPSc.

    3. Mutation of the PrP gene resulting in PrPSc production.

Pathological Consequences

  • Accumulation of protease-resistant PrPSc leads to grey matter vacuolation and associated pathological changes.

  • PrPSc predominantly features a β-sheet structure, capable of converting normal α-helical PrPC into pathological forms.

Types of Transmissible Spongiform Encephalopathies

Animal Diseases

  • Scrapie: A chronic infection in sheep, recognized for centuries; persists in equilibrium through horizontal transmission.

  • Bovine Spongiform Encephalopathy (BSE): Neurodegenerative disease first recorded in 1986; involves strict control measures for infected cattle.

  • Feline Spongiform Encephalopathy: Recorded in the early 1990s, related to BSE.

  • Transmissible mink encephalopathy: Linked to scrapie-infected sheep meat.

  • Chronic wasting disease: Affects deer and elk, characterized by severe wasting and trembling.

Human Diseases

  • Kuru: Associated with ritualistic cannibalism in Papua New Guinea.

  • Creutzfeldt-Jakob disease (CJD): Can be sporadic, iatrogenic, or variant; linked to PrP mutations or exposure to contaminated tissues.

Epidemiology and Control of Scrapie

  • Scrapie occurs worldwide (except Australia, New Zealand).

  • Transmission is primarily through ingestion, abrasions, or ewe-to-lamb.

  • Control measures include strict quarantine and slaughter protocols.

Clinical Signs of Scrapie

  • Primarily found in sheep aged 3-4 years.

  • Symptoms include restlessness, tremors, wool loss, emaciation, and often lead to death within 6 months.

  • Mortality rates can range from 3% to 20% in severely affected flocks.

Bovine Spongiform Encephalopathy (BSE)

  • First identified in 1986, with over 180,000 cases confirmed in cattle.

  • Control strategies aim to slaughter infected animals, remove ruminant-derived protein from feed, and conduct thorough cleaning of facilities.

Clinical Signs of BSE

  • Mean incubation period is around 5 years; behavioral changes and weight loss are early indicators.

  • Additional clinical signs include tremors, hyperesthesia, bruxism, and later stages showing ataxia and falling tendencies.

References

  • Pelczar, M.J., Chan, E.C.S., & Krieg, N. (1993). Microbiology. Tata McGraw-Hill.

  • Quinn, P.J. (2011). Veterinary microbiology and microbial disease. Wiley-Blackwell.