TY  - JOUR
AU  - Liu, Shu
AU  - Heumueller, Stefanie-Elisabeth
AU  - Hossinger, André
AU  - Müller, Stephan A
AU  - Buravlova, Oleksandra
AU  - Lichtenthaler, Stefan F
AU  - Denner, Philip
AU  - Vorberg, Ina M
TI  - Reactivated endogenous retroviruses promote protein aggregate spreading.
JO  - Nature Communications
VL  - 14
IS  - 1
SN  - 2041-1723
CY  - [London]
PB  - Nature Publishing Group UK
M1  - DZNE-2023-00808
SP  - 5034
PY  - 2023
AB  - 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.
KW  - Humans
KW  - Endogenous Retroviruses: genetics
KW  - Protein Aggregates
KW  - Amyotrophic Lateral Sclerosis
KW  - Antiviral Agents
KW  - Prions
KW  - Protein Aggregates (NLM Chemicals)
KW  - Antiviral Agents (NLM Chemicals)
KW  - Prions (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:37596282
C2  - pmc:PMC10439213
DO  - DOI:10.1038/s41467-023-40632-z
UR  - https://pub.dzne.de/record/259955
ER  -