Journal Article

DZNE-2023-00808

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Reactivated endogenous retroviruses promote protein aggregate spreading.

Liu, S. (First author)DZNE* ; Heumueller, S.-E. (First author)DZNE* ; Hossinger, A.DZNE* ; Müller, S. A.DZNE* ; Buravlova, O.DZNE* ; Lichtenthaler, S. F.DZNE* ; Denner, P.DZNE* ; Vorberg, I. M. (Last author)DZNE*

2023
Nature Publishing Group UK [London]

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Please use a persistent id in citations: doi:10.1038/s41467-023-40632-z

Abstract: Prion-like spreading of protein misfolding is a characteristic of neurodegenerative diseases, but the exact mechanisms of intercellular protein aggregate dissemination remain unresolved. Evidence accumulates that endogenous retroviruses, remnants of viral germline infections that are normally epigenetically silenced, become upregulated in neurodegenerative diseases such as amyotrophic lateral sclerosis and tauopathies. Here we uncover that activation of endogenous retroviruses affects prion-like spreading of proteopathic seeds. We show that upregulation of endogenous retroviruses drastically increases the dissemination of protein aggregates between cells in culture, a process that can be inhibited by targeting the viral envelope protein or viral protein processing. Human endogenous retrovirus envelopes of four different clades also elevate intercellular spreading of proteopathic seeds, including pathological Tau. Our data support a role of endogenous retroviruses in protein misfolding diseases and suggest that antiviral drugs could represent promising candidates for inhibiting protein aggregate spreading.

Keyword(s): Humans (MeSH) ; Endogenous Retroviruses: genetics (MeSH) ; Protein Aggregates (MeSH) ; Amyotrophic Lateral Sclerosis (MeSH) ; Antiviral Agents (MeSH) ; Prions (MeSH) ; Protein Aggregates ; Antiviral Agents ; Prions

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Contributing Institute(s):

1. Prion Cell Biology (AG Vorberg)
2. Core Research Facilities & Services (AG Fava)
3. Neuroproteomics (AG Lichtenthaler)
4. Laboratory Automation Technologies (LAT) (LAT)

Research Program(s):

1. 352 - Disease Mechanisms (POF4-352) (POF4-352)

Experiment(s):

1. Laboratory Automation Technologies (CRFS-LAT) / Bonn

Appears in the scientific report 2023

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Database coverage:
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Linked articles:

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Dataset Müller, S. A.DZNE* ; Lichtenthaler, S.DZNE*
Dataset: Endogenous retroviruses promote prion-like spreading of proteopathic seeds
PRoteomics IDEntifications Database (2023)2023   Fulltext BibTeX | EndNote: XML, Text | RIS

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