PXD065713-1

PXD065713 is an original dataset announced via ProteomeXchange.

Title	HIV-1 Nef Reprograms Neuronal Lipid Rafts to Drive Neuroinflammation and Neurodegeneration in HIV-associated Neurocognitive Impairment
Description	HIV-associated neurological disorders (HAND) remain a common co-morbidity of HIV infection. HIV protein Nef has been shown to increase the abundance of neuronal lipid rafts - cholesterol- and sphingolipid-rich membrane microdomains implicated in neurodegeneration and neuroinflammation. Here, we investigated how Nef-containing extracellular vesicles (exNef) secreted by glial cells influence the structural and functional properties of neuronal lipid rafts and contribute to HAND pathogenesis. Lipidomics analysis of isolated neuronal lipid raft fractions revealed minimal impact of exNef on the raft lipid composition; physico-chemical properties of the lipid rafts were also unaffected. In contrast, proteomic analysis revealed that among raft proteins with increased abundance following exNef exposure, ～25% were implicated in neurological disease pathways. Notably, this protein signature showed strong concordance with transcriptomic profiles from single-nucleus RNA sequencing (snRNA-seq) of brain from HIV-infected individuals. Targeted protein analysis unveiled that exNef promotes the redistribution of several neurodegenerative and inflammatory proteins to the lipid rafts, resulting in increased inflammation and apoptosis alongside reduced neuronal excitability. Pharmacological disruption of raft elevation with the lipid raft antagonist Oxy210 reversed exNef-induced raft expansion and abrogated these structural and functional alterations. In summary, exNef reorganize the neuronal lipid raft proteome, enhancing the activity of neurodegenerative and inflammatory mediators, thereby contributing to HAND pathogenesis.
HostingRepository	PRIDE
AnnounceDate	2026-03-23
AnnouncementXML	Submission_2026-03-22_17:24:37.298.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Angela Connolly
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2025-07-02 23:45:32	ID requested
⏵ 1	2026-03-22 17:24:38	announced

Fu Y, Huynh K, Mukhamedova N, Crossett B, Tran D, Martinez S, Horvath A, Wang HY, Castello-Serrano I, Ippolitto R, Parhami F, Meikle PJ, Levental I, Bukrinsky M, Sviridov D, Structural and functional modifications of neuronal lipid rafts: implications for HIV-associated neurological disorders. J Neuroinflammation, 23(1):(2026) [pubmed]

10.1186/s12974-026-03730-5;

submitter keyword: Nef, exosomes., neurons,HIV, HIV-associated neurological disorder, lipid rafts, neurodegeneration

Dmitri Sviridov
contact affiliation	Department of Biochemistry and Molecular Biology, Lipoproteins and Atherosclerosis Monash University, Australia Baker Heart and Diabetes Institute, Australia
contact email	dmitri.sviridov@baker.edu.au
lab head
Angela Connolly
contact affiliation	University of Sydney
contact email	aconnolly@sydney.edu.au
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD065713
     1. Label: PRIDE project
     2. Name: HIV-1 Nef Reprograms Neuronal Lipid Rafts to Drive Neuroinflammation and Neurodegeneration in HIV-associated Neurocognitive Impairment