title: Post-conversion sialylation of prions in lymphoid tissues.
abstract: Sialylated glycans on the surface of mammalian cells act as part of a "self-associated molecular pattern," helping the immune system to recognize "self" from "altered self" or "nonself." To escape the host immune system, some bacterial pathogens have evolved biosynthetic pathways for host-like sialic acids, whereas others recruited host sialic acids for decorating their surfaces. Prions lack nucleic acids and are not conventional pathogens. Nevertheless, prions might use a similar strategy for invading and colonizing the lymphoreticular system. Here we show that the sialylation status of the infectious, disease-associated state of the prion protein (PrP(Sc)) changes with colonization of secondary lymphoid organs (SLOs). As a result, spleen-derived PrP(Sc) is more sialylated than brain-derived PrP(Sc). Enhanced sialylation of PrP(Sc) is recapitulated in vitro by incubating brain-derived PrP(Sc) with primary splenocytes or cultured macrophage RAW 264.7 cells. General inhibitors of sialyltranserases (STs), the enzymes that transfer sialic acid residues onto terminal positions of glycans, suppressed extrasialylation of PrP(Sc). A fluorescently labeled precursor of sialic acid revealed ST activity associated with RAW macrophages. This study illustrates that, upon colonization of SLOs, the sialylation status of prions changes by host STs. We propose that this mechanism is responsible for camouflaging prions in SLOs and has broad implications.
authors.affiliation: Center for Biomedical Engineering and Technology, University of Maryland School of Medicine, Baltimore, MD 21201; Department of Anatomy and Neurobiology, University of Maryland School of Medicine, Baltimore, MD 21201;
authors.forename: Saurabh
authors.initials: S
authors.lastname: Srivastava
authors.affiliation: Center for Biomedical Engineering and Technology, University of Maryland School of Medicine, Baltimore, MD 21201; Department of Anatomy and Neurobiology, University of Maryland School of Medicine, Baltimore, MD 21201;
authors.forename: Natallia
authors.initials: N
authors.lastname: Makarava
authors.affiliation: Center for Biomedical Engineering and Technology, University of Maryland School of Medicine, Baltimore, MD 21201; Department of Anatomy and Neurobiology, University of Maryland School of Medicine, Baltimore, MD 21201;
authors.forename: Elizaveta
authors.initials: E
authors.lastname: Katorcha
authors.affiliation: Center for Biomedical Engineering and Technology, University of Maryland School of Medicine, Baltimore, MD 21201; Department of Anatomy and Neurobiology, University of Maryland School of Medicine, Baltimore, MD 21201;
authors.forename: Regina
authors.initials: R
authors.lastname: Savtchenko
authors.affiliation: Biochemistry Center, University of Heidelberg, 69120 Heidelberg, Germany.
authors.forename: Reinhard
authors.initials: R
authors.lastname: Brossmer
authors.affiliation: Center for Biomedical Engineering and Technology, University of Maryland School of Medicine, Baltimore, MD 21201; Department of Anatomy and Neurobiology, University of Maryland School of Medicine, Baltimore, MD 21201; baskakov@umaryland.edu.
authors.forename: Ilia V
authors.initials: IV
authors.lastname: Baskakov
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism; D015180:Electrophoresis, Gel, Two-Dimensional; D005260:Female; D008221:Lymphoid Tissue / Q000378:metabolism*; D008264:Macrophages / Q000378:metabolism; D008647:Mesocricetus; D051379:Mice; D008810:Mice, Inbred C57BL; D018621:PrPC Proteins / Q000737:chemistry / Q000378:metabolism*; D018620:PrPSc Proteins / Q000737:chemistry / Q000378:metabolism*; D017096:Prion Diseases / Q000378:metabolism*; D011499:Protein Processing, Post-Translational; D000067996:RAW 264.7 Cells; D012608:Scrapie / Q000378:metabolism; D012794:Sialic Acids / Q000737:chemistry; D013154:Spleen / Q000166:cytology / Q000378:metabolism
chemical_list: D018621:PrPC Proteins; D018620:PrPSc Proteins; D012794:Sialic Acids
keywords: macrophages; prion diseases; prions; sialic acid; sialylated glycans