TRIM21-IgG Colocalization in Placentas Exposed to HIV-1

Even when maternal HIV-1 infection is controlled with antiretroviral therapy (ART), the placenta may maintain specialized antiviral defenses. A study published in Frontiers in Immunology examined how tripartite motif (TRIM) proteins, a family of immune-regulatory proteins, contribute to placental immunity in women living with HIV-1. The findings identified increased expression of several TRIM proteins and enrichment of TRIM21 alongside immunoglobulin G (IgG) within placental villi, suggesting a potential interaction between innate and antibody-mediated immunity.

Examining Placental Immune Activity
Researchers in Brazil compared placental samples from 15 women living with HIV-1 and receiving ART and 18 uninfected controls. Ten women in the HIV-1 group had undetectable viral loads at delivery, while five had detectable viremia.

Using quantitative real-time polymerase chain reaction (RT-qPCR), investigators measured the expression of seven TRIM genes in two placental compartments: the maternal decidua and fetal-derived chorionic villi. Additional analyses included histopathology, computational gene-network modeling, and confocal immunofluorescence microscopy to assess TRIM21 and IgG localization.

Distinct Antiviral Responses Across Placental Compartments
Gene-expression analysis revealed significant differences between the groups:

• Decidua: TRIM21, TRIM39, and TRIM64B expression were significantly increased in the HIV-1 group.
• Chorionic villi: TRIM21 and TRIM39 expression were significantly increased, while TRIM64B and TRIM71 were undetectable in both groups.

Computational network analysis linked these proteins to pathways involved in ubiquitination, type I interferon signaling, cytokine regulation, and antiviral immune responses. However, expression of SAMHD1, an antiviral restriction factor that TRIM21 can regulate in other viral infections, remained comparable between groups despite previous evidence that TRIM21 can regulate this antiviral restriction factor during other viral infections.

Histopathological examination of six placentas per group revealed no acute or chronic inflammatory lesions. However, features of maternal vascular malperfusion were more frequent in the HIV-1 group, including villous hypoplasia (83.3% versus 50.0%) and syncytial knots (66.7% versus 33.3%).

TRIM21 and IgG Colocalization Emerges as a Key Finding
The most notable finding involved the spatial relationship between TRIM21 and maternal IgG.

Confocal immunofluorescence demonstrated significantly greater TRIM21 and IgG fluorescence, along with increased colocalization of the two proteins, within chorionic villi from women living with HIV-1. These differences were not observed in the decidua.

The investigators propose that TRIM21 may interact with the Fc region of maternal IgG to facilitate intracellular antiviral activity. However, the study did not establish whether the associated antibodies specifically recognized HIV-1 antigens.

Implications for Understanding Placental Protection
These findings suggest that placental antiviral immune activity may remain altered during ART-treated maternal HIV-1 infection, with TRIM21 potentially connecting intracellular immune defenses and maternal antibodies.

Interpretation is limited by the small sample size, observational design, and lack of direct functional evidence demonstrating HIV-1 restriction by TRIM21–IgG interactions. Increased villous IgG could also reflect impaired antibody transfer across the placenta rather than enhanced antiviral activity.

Further research is needed to determine whether these complexes contribute to protection against vertical HIV-1 transmission and whether TRIM21 has implications for neonatal immunity.

Reference:
Campo BN, de Sousa ESA, Pereira NZ, et al. Enrichment of the TRIM21-IgG complex in placental villi during HIV-1 infection. Front Immunol. 2026;17:1922263. doi:10.3389/fimmu.2026.1922263