Reversible off and on Switching of Prion Infectivity Via Removing and Reinstalling Prion Sialylation

Overview

Journal Sci Rep

Specialty Science

Date 2016 Sep 10

PMID 27609323

Citations 20

Authors

Elizaveta Katorcha

Martin L Daus

Nuria Gonzalez-Montalban

Natallia Makarava

Peter Lasch

Michael Beekes

Ilia V Baskakov

Affiliations

Soon will be listed here.

Abstract

The innate immune system provides the first line of defense against pathogens. To recognize pathogens, this system detects a number of molecular features that discriminate pathogens from host cells, including terminal sialylation of cell surface glycans. Mammalian cell surfaces, but generally not microbial cell surfaces, have sialylated glycans. Prions or PrP(Sc) are proteinaceous pathogens that lack coding nucleic acids but do possess sialylated glycans. We proposed that sialylation of PrP(Sc) is essential for evading innate immunity and infecting a host. In this study, the sialylation status of PrP(Sc) was reduced by replicating PrP(Sc) in serial Protein Misfolding Cyclic Amplification using sialidase-treated PrP(C) substrate and then restored to original levels by replication using non-treated substrate. Upon intracerebral administration, all animals that received PrP(Sc) with original or restored sialylation levels were infected, whereas none of the animals that received PrP(Sc) with reduced sialylation were infected. Moreover, brains and spleens of animals from the latter group were completely cleared of prions. The current work established that the ability of prions to infect the host via intracerebral administration depends on PrP(Sc) sialylation status. Remarkably, PrP(Sc) infectivity could be switched off and on in a reversible manner by first removing and then restoring PrP(Sc) sialylation.

Citing Articles

Multiple steps of prion strain adaptation to a new host.

Bocharova O, Makarava N, Pandit N, Molesworth K, Baskakov I Front Neurosci. 2024; 18:1329010.

PMID: 38362022 PMC: 10867973. DOI: 10.3389/fnins.2024.1329010.

Deficiency in ST6GAL1, one of the two α2,6-sialyltransferases, has only a minor effect on the pathogenesis of prion disease.

Makarava N, Katorcha E, Chang J, Lau J, Baskakov I Front Mol Biosci. 2022; 9:1058602.

PMID: 36452458 PMC: 9702343. DOI: 10.3389/fmolb.2022.1058602.

Role of sialylation of N-linked glycans in prion pathogenesis.

Makarava N, Baskakov I Cell Tissue Res. 2022; 392(1):201-214.

PMID: 35088180 PMC: 9329487. DOI: 10.1007/s00441-022-03584-2.

Phagocytic Activities of Reactive Microglia and Astrocytes Associated with Prion Diseases Are Dysregulated in Opposite Directions.

Sinha A, Kushwaha R, Molesworth K, Mychko O, Makarava N, Baskakov I Cells. 2021; 10(7).

PMID: 34359897 PMC: 8304827. DOI: 10.3390/cells10071728.

Site-specific analysis of N-glycans from different sheep prion strains.

Nakic N, Tran T, Novokmet M, Andreoletti O, Lauc G, Legname G PLoS Pathog. 2021; 17(2):e1009232.

PMID: 33600485 PMC: 7891774. DOI: 10.1371/journal.ppat.1009232.

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