Abnormal Vaginal Microbiota Associated with miRNA Targeting the HIV-Host Interactome.

Area of Science:

• Reproductive health
• Microbiology
• Molecular biology
• Immunology

Background:

• Vaginal dysbiosis impacts the mucosal barrier, potentially increasing HIV acquisition risk.
• Micro(mi)-RNAs are endogenous non-coding RNAs with largely unknown roles in female reproductive tract antiviral immunity.
• Understanding miRNA dysregulation by vaginal pathobionts is crucial for HIV prevention strategies.

Purpose of the Study:

• To investigate the role of micro(mi)-RNAs in mediating the effects of vaginal dysbiosis on the mucosal barrier to HIV acquisition.
• To identify specific miRNAs and their target genes dysregulated in bacterial vaginosis (BV).
• To elucidate the mechanism by which BV-associated miRNAs contribute to immune suppression and HIV risk.

Main Methods:

• Analysis of cervicovaginal specimens from 141 women, classifying microbiota by Nugent scoring.
• Shotgun metagenomic sequencing on a subset of 21 women for microbiome classification.
• Quantification of exosomal miRNAs using EdgeSeq-NextGen and differential expression analysis.
• Epigenetic target prediction using MirTarBase and gene ontology enrichment analysis.

Main Results:

• MiRNA profiles significantly differed between normal, intermediate, and bacterial vaginosis (BV) microbiota.
• BV was associated with a higher number of dysregulated miRNAs (588) compared to normal microbiota, targeting over 400 genes.
• BV-dysregulated miRNAs mediated immunosuppressive effects on cytokine levels and targeted genes within the HIV-host interactome.
• Specific miRNAs dysregulated by *G. vaginalis*-dominated microbiomes overlapped significantly with BV-associated miRNAs.

Conclusions:

• Micro(mi)-RNAs dysregulated by vaginal dysbiosis, particularly BV, contribute to immune imbalance.
• These dysregulated miRNAs facilitate cellular pathways exploited by HIV, increasing acquisition risk.
• MiRNA-mediated immune suppression by BV presents a novel mechanism predictive of HIV risk.