Volume 14 Supplement 3

Abstracts from the 2nd International Science Symposium on HIV and Infectious Diseases (HIV SCIENCE 2014)

Open Access

Placental Hofbauer cells assemble and sequester HIV-1 in tetraspanin and DC SIGN positive compartments that are accessible to neutralizing antibodies

  • Erica L Johnson1, 2Email author,
  • Hin Chu1, 2,
  • Siddappa N Byrareddy3,
  • Paul Spearman1, 2 and
  • Rana Chakraborty1, 2
BMC Infectious Diseases201414(Suppl 3):O5

https://doi.org/10.1186/1471-2334-14-S3-O5

Published: 27 May 2014

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.

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.

Authors’ Affiliations

(1)
Department of Pediatrics, Emory University
(2)
Children’s Center for Immunology and Vaccines; Children’s Healthcare of Atlanta
(3)
Department of Pathology & Laboratory Medicine, Emory University School of Medicine, & Emory Vaccine Center

Copyright

© Johnson et al; licensee BioMed Central Ltd. 2014

This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

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