Siglec-1 Is a Novel Dendritic Cell Receptor That Mediates HIV-1 Trans-Infection Through Recognition of Viral Membrane Gangliosides

Izquierdo-Useros, Nuria; Lorizate, Maier; Puertas, María C.; Rodriguez-Plata, Maria T.; Zangger, Nadine; Erikson, Elina; Pino, María; Erkizia, Itziar; Glass, Bärbel; Clotet, Bonaventura; Keppler, Oliver T.; Telenti, Amalio; Kräusslich, Hans‐Georg; Martínez-Picado, Javier

doi:10.1371/journal.pbio.1001448

Cited by 204 publications

(284 citation statements)

References 43 publications

(72 reference statements)

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“…The majority of captured HIV-1 by LPS-matured DCs is Env independent, and binding of HIV-1 occurs via a viral membraneincorporated ganglioside interaction with the cellular Siglec-1 receptor (23)(24)(25). HIV-1 captured by these mDCs end up in a CD81-containing compartment where the virus is protected from degradation.…”

Section: Discussionmentioning

confidence: 99%

“…HIV-1 captured by these mDCs end up in a CD81-containing compartment where the virus is protected from degradation. It could be that HIV-1 binding to Siglec-1 is an evolved mechanism that avoids viral degradation (23).…”

Section: Discussionmentioning

confidence: 99%

“…In contrast, LPS-matured DCs (mDCs) capture HIV-1 predominantly with Siglec-1/CD169, which interacts with sialyllactose-containing gangliosides embedded in the membrane of the virion (23)(24)(25). iDCs can also capture HIV-1 via Siglec-1; however, because of the lower expression of this receptor and the higher expression of C-type lectin receptors, such as DC-SIGN, virus capture is primarily Env dependent.…”

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confidence: 99%

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Reactivation of Neutralized HIV-1 by Dendritic Cells Is Dependent on the Epitope Bound by the Antibody

Montfort

Thomas

Krawczyk

et al. 2015

The Journal of Immunology

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Ab-neutralized HIV-1 can be captured by dendritic cells (DCs), which subsequently transfer infectious HIV-1 to susceptible CD4+ T cells. In this study, we examined the capacity of early Abs, as well as recently identified broadly neutralizing Abs (bNAbs) targeting different envelope glycoprotein (Env) epitopes, to block HIV-1 transmission by immature and mature DCs to HIV-1–sensitive cells. Three bNAbs directed against the gp41 membrane proximal region of Env (2F5, 4E10, and 10E8) and three gp120 bNAbs targeting the CD4 binding site (b12, VRC01, and NIH45-46) were examined. In addition, eight glycan-dependent bNAbs targeting the V1V2 apex (PG9, PG16, and PGT145), the V3 loop (2G12, PGT121, and PGT128), and the gp120–gp41 interface of Env (PGT151 and 35O22) were tested. bNAbs that bound specific glycans showed, depending on the immature or mature state of the DC, diverse efficiencies in HIV-1 trans-infection. All bNAbs that bound the CD4 binding site blocked trans-infection, whereas all bNAbs directed against the membrane proximal region lost neutralizing activity after DC-mediated HIV-1 transmission. To understand how preneutralized HIV-1 can be transferred as infectious virus by DCs, we followed the processing of 2F5-treated HIV-1 by DCs with confocal microscopy. Inhibition of DC-internalization pathways could not reverse the dissociation of 2F5 from HIV-1, suggesting that Ab dissociation occurs directly at the plasma membrane. Collectively, these findings imply that the location of the epitope and the neutralization capacity of these Abs determine the efficiency of DC-mediated HIV-1 transfer.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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Reactivation of Neutralized HIV-1 by Dendritic Cells Is Dependent on the Epitope Bound by the Antibody

Montfort

Thomas

Krawczyk

et al. 2015

The Journal of Immunology

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“…Encapsulation of viral (RNA) genomes in host membranes may be a conserved strategy to protect from antibody-mediated neutralization. There is van Dongen et al some evidence that the human immunodeficiency virus (HIV) can utilize dendritic cell-to-T cell vesicle transfer as an alternative route for productive infection, a mechanism called transinfection (25), which may also be utilized by certain types of EVs (26). Combined, these studies seem to confirm the premise of the Trojan exosome hypothesis that was proposed over a decade ago by Gould et al (27) and was recently adapted (28).…”

mentioning

confidence: 85%

Extracellular Vesicles Exploit Viral Entry Routes for Cargo Delivery

Dongen

Masoumi

Witwer

et al. 2016

Microbiol Mol Biol Rev

226

193

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SUMMARYExtracellular vesicles (EVs) have emerged as crucial mediators of intercellular communication, being involved in a wide array of key biological processes. Eukaryotic cells, and also bacteria, actively release heterogeneous subtypes of EVs into the extracellular space, where their contents reflect their (sub)cellular origin and the physiologic state of the parent cell. Within the past 20 years, presumed subtypes of EVs have been given a rather confusing diversity of names, including exosomes, microvesicles, ectosomes, microparticles, virosomes, virus-like particles, and oncosomes, and these names are variously defined by biogenesis, physical characteristics, or function. The latter category, functions, in particular the transmission of biological signals between cellsin vivoand how EVs control biological processes, has garnered much interest. EVs have pathophysiological properties in cancer, neurodegenerative disorders, infectious disease, and cardiovascular disease, highlighting possibilities not only for minimally invasive diagnostic applications but also for therapeutic interventions, like macromolecular drug delivery. Yet, in order to pursue therapies involving EVs and delivering their cargo, a better grasp of EV targeting is needed. Here, we review recent progress in understanding the molecular mechanisms underpinning EV uptake by receptor-ligand interactions with recipient cells, highlighting once again the overlap of EVs and viruses. Despite their highly heterogeneous nature, EVs require common viral entry pathways, and an unanticipated specificity for cargo delivery is being revealed. We discuss the challenges ahead in delineating specific roles for EV-associated ligands and cellular receptors.

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“…[50][51][52] More experiments should be done in the future to research this point. We also found differences when studying the distribution of HIV-1 particles inside DCs during a transinfection process.…”

mentioning

confidence: 99%

Antiviral mechanism of polyanionic carbosilane dendrimers against HIV-1

Vacas-Córdoba¹,

Malý²,

Mata³

et al. 2016

IJN

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Nanotechnology-derived platforms, such as dendrimers, are very attractive in several biological applications. In the case of human immunodeficiency virus (HIV) infection, polyanionic carbosilane dendrimers have shown great potential as antiviral agents in the development of novel microbicides to prevent the sexual transmission of HIV-1. In this work, we studied the mechanism of two sulfated and naphthylsulfonated functionalized carbosilane dendrimers, G3-S16 and G2-NF16. They are able to inhibit viral infection at fusion and thus at the entry step. Both compounds impede the binding of viral particles to target cell surface and membrane fusion through the blockage of gp120–CD4 interaction. In addition, and for the first time, we demonstrate that dendrimers can inhibit cell-to-cell HIV transmission and difficult infectious synapse formation. Thus, carbosilane dendrimers’ mode of action is a multifactorial process targeting several proteins from viral envelope and from host cells that could block HIV infection at different stages during the first step of infection.

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Siglec-1 Is a Novel Dendritic Cell Receptor That Mediates HIV-1 Trans-Infection Through Recognition of Viral Membrane Gangliosides

Abstract: The novel dendritic cell receptor Siglec-1 binds sialyllactose moieties on HIV-1 membrane gangliosides, thereby enhancing HIV-1 transinfection.

Cited by 204 publications

References 43 publications

Reactivation of Neutralized HIV-1 by Dendritic Cells Is Dependent on the Epitope Bound by the Antibody

Reactivation of Neutralized HIV-1 by Dendritic Cells Is Dependent on the Epitope Bound by the Antibody

Extracellular Vesicles Exploit Viral Entry Routes for Cargo Delivery

Antiviral mechanism of polyanionic carbosilane dendrimers against HIV-1

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