Background
Within monocyte derived macrophages, HIV-1 accumulates in virus containing compartments (VCCs) that are largely inaccessible to the external environment, which implicate these cells as HIV-1 reservoirs. During mother to child transmission, placental macrophages (Hofbauer Cells [HCs]) are viral targets, and have shown to be infected in vivo and sustain low levels of viral replication in vitro, however, the risk of in utero transmission is less than 7%. The role of these primary macrophages as viral reservoirs is largely undefined.
Methods
With consent, term placentas from 20 HIV-1 seronegative women were obtained following caesarian section. VCCs were evaluated with 3D confocal microscopy and correlated with electron microscopy. Co localization R values (Pearson’s correlation) were quantified with co localization module of Volocity5.2.1. Replication kinetics following siRNA and neutralization studies were evaluated using p24 ELISA.
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Results
We demonstrate primary HCs assemble and sequester HIV-1 in VCCs with localization specific to intracellular vesicles and the plasma membrane. These compartments are enriched in endosomal/lysosomal markers, including CD9, CD81, CD63 and LAMP 1, along with DC SIGN. Following internalization, we observed HIV-1 accumulation in acidified compartments. Remarkably, these compartments are accessible via the cell surface and can be targeted by exogenously applied small molecules and HIV-1 specific neutralizing antibodies (NAbs). In addition, broadly NAbs (4E10 and VRC01) neutralized HIV-1 infected HCs and involve the participation of FcγRI for inhibition.
Conclusion
These findings suggest placental HCs possess intrinsic adaptations facilitating sequestration of HIV-1, and may serve as a protective viral reservoir to permit viral degradation, neutralization and antiretroviral drug entry in utero.
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