Abstract
Introduction
Innate immunity constitutes a pivotal defense mechanism protecting the maternal-fetal interface against viral pathogens. However, the dynamics of placental immunity in pregnant women with chronic HIV-1 infection undergoing suppressive antiretroviral therapy (ART) remain poorly understood. Tripartite motif (TRIM) family proteins act as critical host restriction factors or indirect regulators of antiviral pathways through ubiquitination cascades.
Objectives
In this study, we profiled the transcriptional expression of prominent antiviral
TRIM
genes − namely
TRIM5α, TRIM8, TRIM21, TRIM22, TRIM39, TRIM64B,
and
TRIM71
− in both the decidual and chorionic villi compartments of HIV-1-infected parturient women with undetectable viral loads compared to healthy controls (HC).
Methods
Quantitative real-time PCR in the decidua and villi was performed in both the decidual and chorionic villi compartments of HIV-1-infected parturient women compared to HC. Gene network was generated using GeneMANIA was assessed to identify functionally related genes. Given that TRIM21 classically intercepts antibody-coated target complexes, we evaluated its spatial intersection with maternal humoral components via immunofluorescence using a TissueGnostics scanning confocal microscope.
Results
Quantitative real-time PCR revealed compartment-specific alterations, with a significant upregulation of
TRIM21, TRIM39
, and
TRIM64B
in the decidua, and
TRIM21
, and
TRIM39
in the chorionic villi of the HIV-1 group. Systems biology and functional network analyses integrated these central hubs (
TRIM21, TRIM39
and
TRIM64B
) into pathways governing the innate immune response, multi-step protein ubiquitination, type I interferon signaling, response to virus and the regulation of cytokine production. Notably, TRIM21 and IgG protein expressions, along with their physical intracellular colocalization, were significantly enriched exclusively within the placental villi of HIV-1-infected mothers.
Conclusions
Taken together, our findings unveil a localized upregulation of antiviral
TRIM
factors at the maternal-fetal interface and highlight a novel enrichment of TRIM21–IgG complexes within the chorionic villi. This specialized intracellular synergy between innate and humoral mechanisms opens promising avenues for therapeutic and protective strategies against vertical viral transmission.