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α-Synuclein fibrils enhance HIV-1 infection of human T cells, macrophages and microglia

Author

Listed:
  • Lia-Raluca Olari

    (Ulm University Medical Center)

  • Sichen Liu

    (Ulm University Medical Center)

  • Franziska Arnold

    (Ulm University Medical Center)

  • Julia Kühlwein

    (Ulm University)

  • Marta Gil Miró

    (Ulm University Medical Center)

  • Ajeet Rijal Updahaya

    (Center for Clinical Research at the University of Ulm)

  • Christina Stürzel

    (Ulm University Medical Center)

  • Dietmar Rudolf Thal

    (Center for Clinical Research at the University of Ulm
    KU Leuven)

  • Paul Walther

    (Ulm University)

  • Konstantin M. J. Sparrer

    (Ulm University Medical Center
    German Center for Neurodegenerative Diseases (DZNE))

  • Karin M. Danzer

    (Ulm University
    German Center for Neurodegenerative Diseases (DZNE))

  • Jan Münch

    (Ulm University Medical Center)

  • Frank Kirchhoff

    (Ulm University Medical Center)

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.

Suggested Citation

  • Lia-Raluca Olari & Sichen Liu & Franziska Arnold & Julia Kühlwein & Marta Gil Miró & Ajeet Rijal Updahaya & Christina Stürzel & Dietmar Rudolf Thal & Paul Walther & Konstantin M. J. Sparrer & Karin M., 2025. "α-Synuclein fibrils enhance HIV-1 infection of human T cells, macrophages and microglia," Nature Communications, Nature, vol. 16(1), pages 1-18, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-56099-z
    DOI: 10.1038/s41467-025-56099-z
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