MicroRNAs Regulated by Pregnancy Target Antiviral and Cancer Immunity Overlapping with the HIV Interactome

Area of Science:

• Immunology
• Genetics
• Reproductive Biology

Background:

• Innate immunity's role in HIV-1 risk is influenced by reproductive hormones, pregnancy, and lactation, but mechanisms are unclear.
• Pregnancy-associated physiological changes may alter systemic microRNA (miRNA) expression, affecting immunity and infection susceptibility.

Purpose of the Study:

• To investigate how pregnancy-associated physiological adaptations modify systemic miRNA expression.
• To identify pregnancy-specific miRNAs and their targets.
• To explore the relationship between pregnancy-associated miRNAs and the HIV-host interactome.

Main Methods:

• Analysis of 174 serum samples from a longitudinal cohort (Uganda and Zimbabwe) across pre-pregnancy, pregnancy, and postpartum breastfeeding phases.
• Profiling of 2083 cell-free peripheral blood miRNAs using HTG EdgeSeq.
• Identification of differentially expressed (DE) miRNAs and pathway/network analysis using miRWalk, Cytoscape/ClueGO, and cytoHubba.

Main Results:

• Pregnancy was associated with 160 DE miRNAs (29 upregulated, 131 downregulated) targeting 2733 genes.
• Enriched pathways included adaptive immune response, Hippo Signaling, Cellular Senescence, HSV-1 infection, and cancer-related pathways.
• Pregnancy-enriched targets significantly overlapped with the HIV-host interactome, with identified hub genes interacting with HIV-1 proteins (Tat, gp120) and host proteins (HLA-A).

Conclusions:

• Pregnancy-driven systemic miRNAs modulate the HIV-host interactome.
• Specific pregnancy-enriched hub genes are implicated in cell cycle control, viral immune evasion, and replication.
• These findings suggest potential predictive value for miRNAs in HIV acquisition and pathogenesis.