Inactivation of Scrapie Infectivity – Prions

by Vincent Racaniello, PhD

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    00:01 that the scrapie agent was not a virus. On this graph I'm showing you the inactivation curves of different viruses, these are experiments in which different viruses are irradiated and then their infectivity is measured. So on the top line is the inactivation curve of viruses with different size nucleic acid genomes. So the most sensitive to irradiation is herpes simplex virus, that's because it has a very big DNA genome, it's an easy target for irradiation, then you can see lambda DNA, it's irradiation, it requires a little bit more irradiation to inactivate it, because it's genome is a bit smaller and finally polyoma virus with the smallest genome of these DNA viruses, needs even more radiation to inactivate it. So there's a curve of irradiation that increases as the genome gets smaller. We say the target size gets smaller, so you need more irradiation to hit it. The bottom curve shows you the same experiment with RNA viruses. If you have yellow fever with a large RNA genome, it doesn't need a lot of irradiation to inactivate its infectivity, HIV genome is slightly smaller, it needs more irradiation. Now when you put scrapie on this curve, you do the same experiment, you irradiate scrapie with irradiation, you find that it is only inactivated by very high levels of irradiation. So it doesn't behave like any virus, neither a DNA nor an RNA virus and in fact investigators concluded that the scrapie agent probably does not have any nucleic acid in it at all.

    01:45 So around 1967 a mathematician actually named Griffith suggested that the agents of TSEs were in fact pure protein, they had no nucleic acid in them. This proposal was met with a lot of skepticism throughout the scientific world, but in the 1980s Stanley Prusiner identified a single protein in the brain of sheep with scrapie, and showed that this single protein, when purified, could transmit the disease to hamsters. So he purified one protein from a sheep brain, injected it into the hamsters, they developed scrapie, proving that a protein could cause the disease. For this discovery Prusiner was awarded the Nobel Prize in medicine.

    02:33 The current thinking about prions and TSEs is that they are protein-based diseases and in fact the name prion comes from a combination of proteinaceous and infectious. So a prion is a proteinaceous and infectious particle. The protein is encoded by a gene called prnp, and that gene is essential for the pathogenesis of a TSE. So for example you can remove this gene from mice, they are perfectly healthy without it and you can never infect those mice with a prion, they never develop disease. So the protein coding gene is required for development of a TSE.

    About the Lecture

    The lecture Inactivation of Scrapie Infectivity – Prions by Vincent Racaniello, PhD is from the course Microbiology: Introduction.

    Included Quiz Questions

    1. Scrapie
    2. Yellow fever
    3. Herpessimplex
    4. Lambda
    5. Polyoma virus
    1. Herpessimplex
    2. Lambda
    3. Yellow fever
    4. Polyoma virus
    5. Scrapie

    Author of lecture Inactivation of Scrapie Infectivity – Prions

     Vincent Racaniello, PhD

    Vincent Racaniello, PhD

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