Reactivated endogenous retroviruses promote protein aggregate spreading

Shu Liu, Stefanie Elisabeth Heumüller, André Hossinger, Stephan A. Müller, Oleksandra Buravlova, Stefan F. Lichtenthaler, Philip Denner, Ina M. Vorberg

Research output: Contribution to journalArticlepeer-review

4 Scopus citations

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.

Original languageEnglish
Article number5034
JournalNature Communications
Volume14
Issue number1
DOIs
StatePublished - Dec 2023
Externally publishedYes

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