Year: 2025
Type: article
Abstract: 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.
Source: Nature Communications
Language: English
Topic: HIV Research and Treatment
Subfield: Virology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $6,990
Awards: Risk factors for neuropathological hallmark lesions and cell death in preclinical and symptomatic Alzheimer’s disease: a chance for age-of-onset prediction?, G1195029094, G1248857963, G2740218172, G3553959769, G3854543003, Hochauflösendes konfokales Mikroskop für Materialcharakterisierung und Langzeitmessungen, G4868007747, The role of protein aggregate maturation in Alzheimer's disease and other neurodegenerative disorders and its potential for disease monitoring and differential diagnosis.
OpenAlex ID: W4406554349