| Title: |
Identification of proteins in semen-derived extracellular vesicles that bind to Tat and NF-κB and that may impair HIV replication. |
| Authors: |
Okeoma, Bryson C.; Kaddour, Hussein; Naushad, Wasifa; Paromov, Victor; Chaudhary, Ashok; Noghero, Alessio; Stapleton, Jack T.; Okeoma, Chioma M. |
| Source: |
Science Signaling; 9/9/2025, Vol. 18 Issue 903, p1-13, 13p |
| Subject Terms: |
HIV; NF-kappa B; Therapeutics; Semen; Promoters (Genetics); Gene expression; Extracellular vesicles; Protein-protein interactions |
| 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. Editor's summary: Extracellular vesicles from human semen suppress the replication of HIV in culture, at least in part by disrupting the interactions between host and viral transcription factors. Okeoma et al. analyzed the contents of vesicles from donors and identified proteins that interacted with the viral transcriptional activator Tat and the human transcription factor NF-κB subunit p65. Only a few proteins interacted with both factors, and those proteins interacted with larger networks of transcriptional, RNA processing, and epigenetic regulators. These findings may lead to new therapeutics to more durably suppress or even eradicate HIV infection. —Leslie K. Ferrarelli [ABSTRACT FROM AUTHOR] |
| : |
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| Database: |
Complementary Index |