A New Cell Model for Investigating Prion Strain Selection

February 15, 2020 Daniel Y

Prion research

Prion diseases are fatal neurodegenerative diseases that affect humans and animals. Prion strains, conformational variants of misfolded prion proteins, are associated with distinct clinical and pathological phenotypes. Host-strain interactions result in the selective damage of distinct brain areas and they are responsible for strain selection and/or adaptation, but the underlying molecular mechanisms are unknown. Prion strains can be distinguished by their cell tropism in vivo and in vitro, which suggests that susceptibility to distinct prion strains is determined by cellular factors. The neuroblastoma cell line PK1 is refractory to the prion strain Me7, but highly susceptible to RML. We challenged a large number of clonal PK1 lines with Me7 and successfully selected highly Me7-susceptible subclones (PME) to investigate whether the prion strain repertoire of PK1 can be expanded. Notably, the Me7-infected PME clones were more protease-resistant when compared to RML-infected PME clones, which suggested that cell-adapted Me7 and RML are distinct prion strains. Strikingly, Me7-refractory cells, including PK1 and astrocytes in cortico-hippocampal cultures, are highly susceptible to prions, being derived from homogenates of Me7-infected PME cells, suggesting that the passage of Me7 in PME cells leads to an extended host range. Thus, PME clones represent a compelling cell model for strain selection and adaptation.



Have you thought about online lessons?

Online tuition gives you access to brilliant tutors across the country
Connect one-to-one with a tutor or share your lesson with a group for 50% of the tutor's hourly rate! Find a Tutor for One-to-One Find an Online Study Group

Want to know more?

Visit Daniel's profile to find out more and send a message.

Visit Daniel's Profile

Resources others found helpful

KS3 Maths SATS's past papers

Free past SAT's test papers with mark schemes included

learn more

GCSE Exam Papers (new 1-9 specification)

Perfect practice equals top grades!

learn more

How to get into medical school

This resource signposts and describes what we should be aiming for in our application to study …

learn more

Breakfast, lunch, dinner

This is a resource to learn and practice vocabulary on food.

learn more

Free resources, revision notes and past papers for students

Find revision guides, exam papers and sample essays amongst hundreds of free resources available to students.

Find resources any subjects

Maths resources | Science resources | Music resources | Spanish resources | English resources | French resources