TY  - JOUR
AU  - Olari, Lia-Raluca
AU  - Liu, Sichen
AU  - Arnold, Franziska
AU  - Kühlwein, Julia
AU  - Gil Miró, Marta
AU  - Updahaya, Ajeet Rijal
AU  - Stürzel, Christina
AU  - Thal, Dietmar Rudolf
AU  - Walther, Paul
AU  - Sparrer, Konstantin
AU  - Danzer, Karin M
AU  - Münch, Jan
AU  - Kirchhoff, Frank
TI  - α-Synuclein fibrils enhance HIV-1 infection of human T cells, macrophages and microglia.
JO  - Nature Communications
VL  - 16
IS  - 1
SN  - 2041-1723
CY  - [London]
PB  - Springer Nature
M1  - DZNE-2025-00221
SP  - 813
PY  - 2025
AB  - HIV-associated neurocognitive disorders (HAND) and viral reservoirs in the brain remain a significant challenge. Despite their importance, the mechanisms allowing HIV-1 entry and replication in the central nervous system (CNS) are poorly understood. Here, we show that α-synuclein and (to a lesser extent) Aβ fibrils associated with neurological diseases enhance HIV-1 entry and replication in human T cells, macrophages, and microglia. Additionally, an HIV-1 Env-derived amyloidogenic peptide accelerated amyloid formation by α-synuclein and Aβ peptides. Mechanistic studies show that α-synuclein and Aβ fibrils interact with HIV-1 particles and promote virion attachment and fusion with target cells. Despite an overall negative surface charge, these fibrils facilitate interactions between viral and cellular membranes. The enhancing effects of human brain extracts on HIV-1 infection correlated with their binding to Thioflavin T, a dye commonly used to stain amyloids. Our results suggest a detrimental interplay between HIV-1 and brain amyloids that may contribute to the development of neurodegenerative diseases.
KW  - Humans
KW  - alpha-Synuclein: metabolism
KW  - Microglia: metabolism
KW  - Microglia: virology
KW  - HIV-1: physiology
KW  - HIV-1: metabolism
KW  - Macrophages: virology
KW  - Macrophages: metabolism
KW  - T-Lymphocytes: metabolism
KW  - T-Lymphocytes: virology
KW  - T-Lymphocytes: immunology
KW  - Amyloid: metabolism
KW  - HIV Infections: virology
KW  - HIV Infections: metabolism
KW  - HIV Infections: pathology
KW  - Brain: virology
KW  - Brain: metabolism
KW  - Brain: pathology
KW  - Amyloid beta-Peptides: metabolism
KW  - Virus Internalization
KW  - Virus Replication
KW  - Benzothiazoles
KW  - alpha-Synuclein (NLM Chemicals)
KW  - Amyloid (NLM Chemicals)
KW  - Amyloid beta-Peptides (NLM Chemicals)
KW  - thioflavin T (NLM Chemicals)
KW  - Benzothiazoles (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C2  - pmc:PMC11742913
C6  - pmid:39827271
DO  - DOI:10.1038/s41467-025-56099-z
UR  - https://pub.dzne.de/record/276149
ER  -