Enrichment of the TRIM21-IgG complex in placental villi during HIV-1 infection.

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.