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

• Type of Material: Article
• Authors: Erica L. Johnson, Emory University; Hin Chu, Emory University; Siddappa Byrareddy, Emory University; Paul Spearman, Emory University; Rana Chakraborty, Emory University
• Language: English
• Date: 2015-01-22
• Publisher: BioMed Central
• Publication Version: Final Published Version
• Copyright Statement: © 2015 Johnson EL et al; licensee International AIDS Society
• License: Creative Commons Attribution 3.0 Unported
• Final Published Version (URL): http://dx.doi.org/10.7448/IAS.18.1.19385
• Title of Journal or Parent Work: Journal of the International AIDS Society
• ISSN: 1758-2652
• Volume: 18
• Issue: 1
• Start Page: 19385
• End Page: 19385
• Grant/Funding Information: This work was supported in part by the Robert P. Apkarian Integrated Electron Microscopy Core.; This research was supported by the Emory Center for AIDS Research (grant number P30AI050409) and the Emory Medical Care Foundation.
• Keywords: PLASMA-MEMBRANE; REPLICATION; HUMAN-IMMUNODEFICIENCY-VIRUS; TRANSMISSION; INFECTION; HIV-1; Science & Technology; DENDRITIC CELLS; IN-UTERO; LATE ENDOSOMES; MACROPHAGES; T-CELLS; Infectious Diseases; bNAbs; VCCs; Hofbauer cells; placenta; MTCT; Life Sciences & Biomedicine; Immunology
• Research Categories: Health Sciences, Obstetrics and Gynecology; Health Sciences, Epidemiology

Abstract

Introduction: Within monocyte-derived macrophages, HIV-1 accumulates in intracellular virus-containing compartments (VCCs) that are inaccessible to the external environment, which implicate these cells as latently infected HIV-1 reservoirs. During mother-to-child transmission of HIV-1, human placental macrophages (Hofbauer cells (HCs)) are viral targets, and have been 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. The objective of this study is to define potential sites of viral assembly, accumulation and neutralization in HCs given the pivotal role of the placenta in preventing HIV-1 infection in the mother-infant dyad. Methods: Term placentae from 20 HIV-1 seronegative women were obtained following caesarian section. VCCs were evaluated by 3D confocal and electron microscopy. Colocalization R values (Pearson's correlation) were quantified with colocalization module of Volocity 5.2.1. Replication kinetics and neutralization studies were evaluated using p24 ELISA. Results: We demonstrate that primary HCs assemble and sequester HIV-1BaL in intracellular VCCs, which are enriched in endosomal/lysosomal markers, including CD9, CD81, CD63 and LAMP-1. Following infection, we observed HIV-1 accumulation in potentially acidic compartments, which stained intensely with Lysotracker-Red. Remarkably, these compartments are readily accessible via the cell surface and can be targeted by exogenously applied small molecules and HIV-1-specific broadly neutralizing antibodies. In addition, broadly neutralizing antibodies (4E10 and VRC01) limited viral replication by HIV-1-infected HCs, which may be mediated by FcγRI. Conclusions: These findings suggest that placental HCs possess intrinsic adaptations facilitating unique sequestration of HIV-1, and may serve as a protective viral reservoir to permit viral neutralization and/or antiretroviral drug entry in utero.