Journal article
Identification of proteins in semen-derived extracellular vesicles that bind to Tat and NF-κB and that may impair HIV replication
Science signaling, Vol.18(903), eado9243
09/09/2025
DOI: 10.1126/scisignal.ado9243
PMCID: PMC13249011
PMID: 40924817
Abstract
Replication of HIV-1 requires the coordinated action of host and viral transcription factors, most critically the viral transactivator Tat and the host nuclear factor κB (NF-κB). This activity is disrupted in infected cells that are cultured with extracellular vesicles (EVs) present in human semen, suggesting that they contain factors that could inform the development of new therapeutics. Here, we explored the contents of semen-derived EVs (SEVs) from uninfected donors and individuals with HIV-1 and identified host proteins that interacted with HIV Tat and the NF-κB subunit p65. Integrative network and pathway enrichment analyses of these complexes revealed associations with an array of biological functions regulating gene expression. Several proteins in SEVs bound to both Tat and NF-κB p65: the scaffolding and cell signaling regulatory protein AKAP9, the G protein signaling regulator ARHGEF28, the epigenetic reader BRD2, the small nuclear RNA processor INTS1, and the transcription elongation inhibitor NELFB. When complexed with p65, NELFB also interacted with HEXIM1, another transcription elongation inhibitor, suggesting that SEVs may inhibit HIV-1 propagation through multiple networks of transcriptional activation and repression. Exploring these data and the underlying mechanisms may inform the development of more effective or more durable therapeutics against HIV.
Details
- Title: Subtitle
- Identification of proteins in semen-derived extracellular vesicles that bind to Tat and NF-κB and that may impair HIV replication
- Creators
- Bryson C Okeoma - New York Medical CollegeHussein Kaddour - Stony Brook UniversityWasifa Naushad - New York Medical CollegeVictor Paromov - Meharry Medical CollegeAshok Chaudhary - Medical Service, Iowa City Veterans Affairs Medical Center, University of Iowa, 604 Highway 6, Iowa City, IA 52246-2208, USAAlessio Noghero - Lovelace Biomedical Institute, Albuquerque, NM 87108-5127, USAJack T Stapleton - University of IowaChioma M Okeoma - New York Medical College
- Resource Type
- Journal article
- Publication Details
- Science signaling, Vol.18(903), eado9243
- DOI
- 10.1126/scisignal.ado9243
- PMID
- 40924817
- PMCID
- PMC13249011
- NLM abbreviation
- Sci Signal
- ISSN
- 1945-0877
- eISSN
- 1937-9145
- Publisher
- AMER ASSOC ADVANCEMENT SCIENCE
- Grant note
- NIH grants: R01DA042348-01, R01DA050169, R21/R33DA053643 Veterans Affairs (VA) Merit Review: BX000207 Startup funds from New York Medical College (NYMC)Lovelace Biomedical
This study was supported by NIH grants R01DA042348-01, R01DA050169, and R21/R33DA053643 (to C.M.O.), by the Veterans Affairs (VA) Merit Review BX000207 (to J.T.S.), and by startup funds from New York Medical College (NYMC) and Lovelace Biomedical.
- Language
- English
- Date published
- 09/09/2025
- Academic Unit
- Microbiology and Immunology; Infectious Diseases; Internal Medicine
- Record Identifier
- 9984961011802771
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