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000276149 1001_ $$00000-0001-7793-4408$$aOlari, Lia-Raluca$$b0
000276149 245__ $$aα-Synuclein fibrils enhance HIV-1 infection of human T cells, macrophages and microglia.
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000276149 520__ $$aHIV-associated neurocognitive disorders (HAND) and viral reservoirs in the brain remain a significant challenge. Despite their importance, the mechanisms allowing HIV-1 entry and replication in the central nervous system (CNS) are poorly understood. Here, we show that α-synuclein and (to a lesser extent) Aβ fibrils associated with neurological diseases enhance HIV-1 entry and replication in human T cells, macrophages, and microglia. Additionally, an HIV-1 Env-derived amyloidogenic peptide accelerated amyloid formation by α-synuclein and Aβ peptides. Mechanistic studies show that α-synuclein and Aβ fibrils interact with HIV-1 particles and promote virion attachment and fusion with target cells. Despite an overall negative surface charge, these fibrils facilitate interactions between viral and cellular membranes. The enhancing effects of human brain extracts on HIV-1 infection correlated with their binding to Thioflavin T, a dye commonly used to stain amyloids. Our results suggest a detrimental interplay between HIV-1 and brain amyloids that may contribute to the development of neurodegenerative diseases.
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000276149 650_7 $$2NLM Chemicals$$aalpha-Synuclein
000276149 650_7 $$2NLM Chemicals$$aAmyloid
000276149 650_7 $$2NLM Chemicals$$aAmyloid beta-Peptides
000276149 650_7 $$02390-54-7$$2NLM Chemicals$$athioflavin T
000276149 650_7 $$2NLM Chemicals$$aBenzothiazoles
000276149 650_2 $$2MeSH$$aHumans
000276149 650_2 $$2MeSH$$aalpha-Synuclein: metabolism
000276149 650_2 $$2MeSH$$aMicroglia: metabolism
000276149 650_2 $$2MeSH$$aMicroglia: virology
000276149 650_2 $$2MeSH$$aHIV-1: physiology
000276149 650_2 $$2MeSH$$aHIV-1: metabolism
000276149 650_2 $$2MeSH$$aMacrophages: virology
000276149 650_2 $$2MeSH$$aMacrophages: metabolism
000276149 650_2 $$2MeSH$$aT-Lymphocytes: metabolism
000276149 650_2 $$2MeSH$$aT-Lymphocytes: virology
000276149 650_2 $$2MeSH$$aT-Lymphocytes: immunology
000276149 650_2 $$2MeSH$$aAmyloid: metabolism
000276149 650_2 $$2MeSH$$aHIV Infections: virology
000276149 650_2 $$2MeSH$$aHIV Infections: metabolism
000276149 650_2 $$2MeSH$$aHIV Infections: pathology
000276149 650_2 $$2MeSH$$aBrain: virology
000276149 650_2 $$2MeSH$$aBrain: metabolism
000276149 650_2 $$2MeSH$$aBrain: pathology
000276149 650_2 $$2MeSH$$aAmyloid beta-Peptides: metabolism
000276149 650_2 $$2MeSH$$aVirus Internalization
000276149 650_2 $$2MeSH$$aVirus Replication
000276149 650_2 $$2MeSH$$aBenzothiazoles
000276149 7001_ $$00009-0006-1023-9076$$aLiu, Sichen$$b1
000276149 7001_ $$aArnold, Franziska$$b2
000276149 7001_ $$0P:(DE-2719)9001523$$aKühlwein, Julia$$b3$$udzne
000276149 7001_ $$aGil Miró, Marta$$b4
000276149 7001_ $$aUpdahaya, Ajeet Rijal$$b5
000276149 7001_ $$aStürzel, Christina$$b6
000276149 7001_ $$00000-0002-1036-1075$$aThal, Dietmar Rudolf$$b7
000276149 7001_ $$aWalther, Paul$$b8
000276149 7001_ $$0P:(DE-2719)9003481$$aSparrer, Konstantin$$b9$$udzne
000276149 7001_ $$0P:(DE-2719)9001513$$aDanzer, Karin M$$b10
000276149 7001_ $$00000-0001-7316-7141$$aMünch, Jan$$b11
000276149 7001_ $$00000-0002-7052-2360$$aKirchhoff, Frank$$b12
000276149 773__ $$0PERI:(DE-600)2553671-0$$a10.1038/s41467-025-56099-z$$gVol. 16, no. 1, p. 813$$n1$$p813$$tNature Communications$$v16$$x2041-1723$$y2025
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