α-Synuclein fibrils enhance HIV-1 infection of human T cells, macrophages and microglia
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...
Saved in:
| Main Authors: | , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2025-01-01
|
| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-025-56099-z |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1832594591782535168 |
|---|---|
| author | 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. Danzer Jan Münch Frank Kirchhoff |
| author_facet | 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. Danzer Jan Münch Frank Kirchhoff |
| author_sort | Lia-Raluca Olari |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-f439b62f41434b9a81acdfa533318c05 |
| institution | Kabale University |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-f439b62f41434b9a81acdfa533318c052025-01-19T12:32:00ZengNature PortfolioNature Communications2041-17232025-01-0116111810.1038/s41467-025-56099-zα-Synuclein fibrils enhance HIV-1 infection of human T cells, macrophages and microgliaLia-Raluca Olari0Sichen Liu1Franziska Arnold2Julia Kühlwein3Marta Gil Miró4Ajeet Rijal Updahaya5Christina Stürzel6Dietmar Rudolf Thal7Paul Walther8Konstantin M. J. Sparrer9Karin M. Danzer10Jan Münch11Frank Kirchhoff12Institute of Molecular Virology, Ulm University Medical CenterInstitute of Molecular Virology, Ulm University Medical CenterInstitute of Molecular Virology, Ulm University Medical CenterDepartment of Neurology, Ulm UniversityInstitute of Molecular Virology, Ulm University Medical CenterLaboratory of Neuropathology, Institute of Pathology, Center for Clinical Research at the University of UlmInstitute of Molecular Virology, Ulm University Medical CenterLaboratory of Neuropathology, Institute of Pathology, Center for Clinical Research at the University of UlmCentral Facility for Electron Microscopy, Ulm UniversityInstitute of Molecular Virology, Ulm University Medical CenterDepartment of Neurology, Ulm UniversityInstitute of Molecular Virology, Ulm University Medical CenterInstitute of Molecular Virology, Ulm University Medical CenterAbstract 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.https://doi.org/10.1038/s41467-025-56099-z |
| spellingShingle | 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. Danzer Jan Münch Frank Kirchhoff α-Synuclein fibrils enhance HIV-1 infection of human T cells, macrophages and microglia Nature Communications |
| title | α-Synuclein fibrils enhance HIV-1 infection of human T cells, macrophages and microglia |
| title_full | α-Synuclein fibrils enhance HIV-1 infection of human T cells, macrophages and microglia |
| title_fullStr | α-Synuclein fibrils enhance HIV-1 infection of human T cells, macrophages and microglia |
| title_full_unstemmed | α-Synuclein fibrils enhance HIV-1 infection of human T cells, macrophages and microglia |
| title_short | α-Synuclein fibrils enhance HIV-1 infection of human T cells, macrophages and microglia |
| title_sort | α synuclein fibrils enhance hiv 1 infection of human t cells macrophages and microglia |
| url | https://doi.org/10.1038/s41467-025-56099-z |
| work_keys_str_mv | AT liaralucaolari asynucleinfibrilsenhancehiv1infectionofhumantcellsmacrophagesandmicroglia AT sichenliu asynucleinfibrilsenhancehiv1infectionofhumantcellsmacrophagesandmicroglia AT franziskaarnold asynucleinfibrilsenhancehiv1infectionofhumantcellsmacrophagesandmicroglia AT juliakuhlwein asynucleinfibrilsenhancehiv1infectionofhumantcellsmacrophagesandmicroglia AT martagilmiro asynucleinfibrilsenhancehiv1infectionofhumantcellsmacrophagesandmicroglia AT ajeetrijalupdahaya asynucleinfibrilsenhancehiv1infectionofhumantcellsmacrophagesandmicroglia AT christinasturzel asynucleinfibrilsenhancehiv1infectionofhumantcellsmacrophagesandmicroglia AT dietmarrudolfthal asynucleinfibrilsenhancehiv1infectionofhumantcellsmacrophagesandmicroglia AT paulwalther asynucleinfibrilsenhancehiv1infectionofhumantcellsmacrophagesandmicroglia AT konstantinmjsparrer asynucleinfibrilsenhancehiv1infectionofhumantcellsmacrophagesandmicroglia AT karinmdanzer asynucleinfibrilsenhancehiv1infectionofhumantcellsmacrophagesandmicroglia AT janmunch asynucleinfibrilsenhancehiv1infectionofhumantcellsmacrophagesandmicroglia AT frankkirchhoff asynucleinfibrilsenhancehiv1infectionofhumantcellsmacrophagesandmicroglia |