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000259955 1001_ $$0P:(DE-2719)2810461$$aLiu, Shu$$b0$$eFirst author$$udzne
000259955 245__ $$aReactivated endogenous retroviruses promote protein aggregate spreading.
000259955 260__ $$a[London]$$bNature Publishing Group UK$$c2023
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000259955 520__ $$aPrion-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.
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000259955 650_2 $$2MeSH$$aHumans
000259955 650_2 $$2MeSH$$aEndogenous Retroviruses: genetics
000259955 650_2 $$2MeSH$$aProtein Aggregates
000259955 650_2 $$2MeSH$$aAmyotrophic Lateral Sclerosis
000259955 650_2 $$2MeSH$$aAntiviral Agents
000259955 650_2 $$2MeSH$$aPrions
000259955 650_7 $$2NLM Chemicals$$aProtein Aggregates
000259955 650_7 $$2NLM Chemicals$$aAntiviral Agents
000259955 650_7 $$2NLM Chemicals$$aPrions
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000259955 7001_ $$0P:(DE-2719)9001081$$aHeumueller, Stefanie-Elisabeth$$b1$$eFirst author$$udzne
000259955 7001_ $$0P:(DE-2719)2810581$$aHossinger, André$$b2$$udzne
000259955 7001_ $$0P:(DE-2719)2810938$$aMüller, Stephan A$$b3
000259955 7001_ $$0P:(DE-2719)2812777$$aBuravlova, Oleksandra$$b4$$udzne
000259955 7001_ $$0P:(DE-2719)2181459$$aLichtenthaler, Stefan F$$b5
000259955 7001_ $$0P:(DE-2719)2810245$$aDenner, Philip$$b6$$udzne
000259955 7001_ $$0P:(DE-2719)2481765$$aVorberg, Ina M$$b7$$eLast author
000259955 773__ $$0PERI:(DE-600)2553671-0$$a10.1038/s41467-023-40632-z$$gVol. 14, no. 1, p. 5034$$n1$$p5034$$tNature Communications$$v14$$x2041-1723$$y2023
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