Virology Weekly Newsletter 22.03.2013 – Bumper End of Term Prion Edition!

Principles of molecular virology Students taking my virology course at the University of Leicester get a weekly newsletter containing extra links relevant to the lectures. This week we have been looking at sub-viral agents and the class notes are from Principles of Molecular Virology, chapter 10.

 

 

The Importance of Prions. (2013) PLoS Pathogens 9(1): e1003090
While agent host-range and strain properties convinced early researchers of a viral etiology, the once unorthodox postulate that prion transmission occurs by conformational corruption of host-encoded cellular prion protein (PrPC) by a pathogenic isoform (PrPSc) is now widely accepted. Indeed, conformational templating is increasingly understood to be a general mechanism of protein-mediated information transfer and pathogenesis. The high infectivity of prions, their capacity to cause neurodegeneration in genetically tractable animal models, as well as the ability to culture prions in cells, or under cell-free conditions using defined components, provide finely controlled experimental settings in which to elucidate general mechanisms for all diseases involving protein conformational templating, and thus to develop integrated therapeutic approaches.

Unusual infectious agents

Proteins behind mad-cow disease also help brain to develop
Prions are best known as the infectious agents that cause ‘mad cow’ disease and the human versions of it, such as variant Creutzfeldt–Jakob disease. But the proteins also have at least one known useful function, in the cells that insulate nerves, and are suspected to have more. Now researchers have provided the first direct evidence that the proteins play an important role in neurons themselves, lending a hand in forming neuronal connections.

Susan Lindquist: Protein Folding and Prions

Behavior of Prions in the Environment: Implications for Prion Biology. (2013) PLoS Pathogens 9(2): e1003113
The basic parameters of prion environmental interactions are only beginning to be described, and the effect of these interactions on prion transmission and pathogenesis are poorly understood. The interaction of prions in the environment is complex and must include consideration of the route of introduction for prions to the environment as well as the effects of soil properties and prion strain on prion interaction with soil. Once bound to soil, prions do not readily disassociate from the soil particle and remain highly infectious. The implications of these important observations are that prions immobilized to soil may persist at the surface where transmission to a naïve host would be more likely to occur. Strain-specific interactions with the environment may result in preferential selection of strains that have properties that favor environmental persistence and transmission.

Kuru: The Science and The Sorcery

Acquisition of Drug Resistance and Dependence by Prions. (2013) PLoS Pathogens 9(2): e1003158
Prions consist of PrPSc, an aggregated conformer of the host protein PrPC. PrPSc multiplies by catalyzing the conformational conversion of PrPC into a likeness of itself. Prions present as distinct strains that have the same primary amino acid sequence but differ in their conformation. Many distinct mouse-derived prions strains, for example RML, 22L or Me7, have been isolated. Prions can adapt to their environment. We investigated whether propagation of swainsonine-sensitive RML prions in the presence of the drug would yield swainsonine-resistant variants. Propagation of prions in the presence of an inhibitory drug may not only cause the selection of drug-resistant prions but even of stable prion variants that propagate more efficiently in the presence of the drug. These adaptations are most likely due to conformational changes of the abnormal prion protein.

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