Sialyllactose in Viral Membrane Gangliosides Is a Novel Molecular Recognition Pattern for Mature Dendritic Cell Capture of HIV-1

Izquierdo-Useros, Nuria; Lorizate, Maier; Contreras, F.‐Xabier; Rodriguez-Plata, Maria T.; Glass, Bärbel; Erkizia, Itziar; Prado, Julia G.; Casas, Josefina; Fabriás, Gemma; Kräusslich, Hans‐Georg; Martínez-Picado, Javier

doi:10.1371/journal.pbio.1001315

Cited by 76 publications

(107 citation statements)

References 73 publications

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“…However, these studies also highlighted the fact that trans-infection is not per se dependent upon viral component recognition. Indeed, Siglec-1 has also been identified as the receptor for exosomes (131,134). This finding shed light on earlier studies showing that HIV-1 trafficking in infected cells or in mature MDDCs was very similar to that of exosomes (120).…”

Section: Figsupporting

confidence: 69%

Cell-Free versus Cell-to-Cell Infection by Human Immunodeficiency Virus Type 1 and Human T-Lymphotropic Virus Type 1: Exploring the Link among Viral Source, Viral Trafficking, and Viral Replication

Dutartre

Claviere

Journo

et al. 2016

J Virol

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Human immunodeficiency virus type 1 (HIV-1) and human T-lymphotropic virus type 1 (HTLV-1) are complex retroviruses mainly infecting CD4؉ T lymphocytes. In addition, antigen-presenting cells such as dendritic cells (DCs) are targeted in vivo by both viruses, although to a lesser extent. Interaction of HIV-1 with DCs plays a key role in viral dissemination from the mucosa to CD4؉ T lymphocytes present in lymphoid organs. While similar mechanisms may occur for HTLV-1 as well, most HTLV-1 data were obtained from T-cell studies, and little is known regarding the trafficking of this virus in DCs. We first compared the efficiency of cell-free versus cell-associated viral sources of both retroviruses at infecting DCs. We showed that both HIV-1 and HTLV-1 cell-free particles are poorly efficient at productively infecting DCs, except when DC-SIGN has been engaged. Furthermore, while SAMHD-1 accounts for restriction of cell-free HIV-1 infection, it is not involved in HTLV-1 restriction. In addition, cell-free viruses lead mainly to a nonproductive DC infection, leading to trans-infection of T-cells, a process important for HIV-1 spread but not for that of HTLV-1. Finally, we show that T-DC cell-to-cell transfer implies viral trafficking in vesicles that may both increase productive infection of DCs ("cis-infection") and allow viral escape from immune surveillance. Altogether, these observations allowed us to draw a model of HTLV-1 and HIV-1 trafficking in DCs. Human T-lymphotropic virus type 1 (HTLV-1) and human immunodeficiency virus type 1 (HIV-1) infect 5 to 10 million (1) and 30 million (2) individuals worldwide, respectively. HTLV-1 is present in clusters of high endemicity such as in Japan, intertropical Africa, the Caribbean, and South America (3), whereas HIV-1 is pandemic. Interestingly, while both viruses infect CD4 ϩ T cells in vivo, the consequences of infection are opposite. After a long period of clinical latency, HTLV-1 infection leads either to adult T-cell leukemia (ATL) (4), an uncontrolled CD4 ϩ T lymphocyte proliferation with a very poor prognosis, or to an inflammatory disorder named HTLV-1-associated myelopathy/ tropical spastic paraparesis (HAM/TSP) in a fraction of infected individuals (5). On the other hand, HIV-1 is associated with CD4 ϩ T-lymphocyte death and causes AIDS (for a review, see reference 6).Interestingly, both viruses also infect antigen-presenting cells (APCs) to a lesser extent, among which are different subtypes of dendritic cells (DCs), such as myeloid DCs, monocyte-derived DCs (MDDCs), and plasmacytoid DCs (pDCs) (7-10). After viral entry in mucosal tissues during sexual intercourse or breastfeeding (11,12), DCs can be used as viral carriers, thus allowing the virus to reach lymphoid organs, where it infects CD4 ϩ T lymphocytes (13). Thus, both retroviruses may hijack (i) the ability of DCs to capture pathogens and (ii) their vesicular traffic pathways in order to be transmitted to target cells without requiring a productive viral cycle (i.e., by trans-infection of T cells). tra...

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Section: Figsupporting

confidence: 69%

Cell-Free versus Cell-to-Cell Infection by Human Immunodeficiency Virus Type 1 and Human T-Lymphotropic Virus Type 1: Exploring the Link among Viral Source, Viral Trafficking, and Viral Replication

Dutartre

Claviere

Journo

et al. 2016

J Virol

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“…Expression of the HIV-1 Gag-eGFP fusion protein alone is sufficient for the formation of eGFP-containing fluorescent VLPs that assemble and bud from regions within the cell in a manner indistinguishable from that observed for replication-competent wild-type HIV-1 (66,67). Using this FACS-based assay, we and others have determined that the GSLs GM1 and GM3 are necessary for HIV-1 to be captured by mature DCs (15,17) in a CD169-dependent manner (14,16).…”

Section: Resultsmentioning

confidence: 88%

“…Recently, we and others have identified CD169 (Siglec-1) to be the receptor on DCs which captures HIV-1 particles in a gp120-independent, GM3-dependent manner (14)(15)(16)(17). Furthermore, CD169 was shown to be predominantly responsible for mature DC (MDC)-mediated HIV-1 trans infection (14,16).…”

mentioning

confidence: 99%

Virus Particle Release from Glycosphingolipid-Enriched Microdomains Is Essential for Dendritic Cell-Mediated Capture and Transfer of HIV-1 and Henipavirus

Akiyama

Miller

Patel

et al. 2014

J Virol

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Human immunodeficiency virus type 1 (HIV-1) exploits dendritic cells (DCs) to promote its transmission to T cells. We recently lentivirus particles by MDCs were severely attenuated upon depletion of GSLs from virus particles. These results suggest that GSL incorporation into virions is critical for the interaction of diverse enveloped RNA viruses with DCs and that the GSL-CD169 recognition nexus might be a conserved viral mechanism of parasitization of DC functions for systemic virus dissemination. IMPORTANCEDendritic cells (DCs) can capture HIV-1 particles and transfer captured virus particles to T cells without establishing productive infection in DCs, a mechanism of HIV-1 trans infection. We have recently identified CD169-mediated recognition of GM3, a host-derived glycosphingolipid (GSL) incorporated into the virus particle membrane, as the receptor and ligand for the DC-HIV trans infection pathway. In this study, we have identified the matrix (MA) domain of Gag to be the viral determinant that governs incorporation of GM3 into HIV-1 particles, a previously unappreciated function of the HIV-1 MA. In addition, we demonstrate that the GSL-CD169-dependent trans infection pathway is also utilized as a dissemination mechanism by henipaviruses. GSL incorporation in henipaviruses was also dependent on the viral capsid (M) protein-directed assembly and budding from GSL-enriched lipid microdomains. These findings provide evidence of a conserved mechanism of retrovirus and henipavirus parasitization of cell-to-cell recognition pathways for systemic virus dissemination.

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“…Proinflammatory (e.g., stimulation of CD11c+ dendritic cells 22 ) as well as anti-inflammatory (e.g., inhibition of cholera toxin 23 ) properties have been ascribed to this sialylated component that is also found in milk (HMDB00825). Also, sialyllactose may represent a molecular recognition pattern for dendritic cell capture 24 and contribute to alloantigen presentation and triggering of acute rejection. Changes in sialyllactose levels have been noted in cells grown under bioenergetic or oxidative stress (S. Gross, unpublished observations), and their increased levels during ACR may represent aberrant membrane glycolipid metabolism in immune and/or kidney parenchymal cells.…”

Section: Discussionmentioning

confidence: 99%

Urine Metabolite Profiles Predictive of Human Kidney Allograft Status

Suhre

Schwartz

Sharma

et al. 2016

Journal of the American Society of Nephrology

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Noninvasive diagnosis and prognostication of acute cellular rejection in the kidney allograft may help realize the full benefits of kidney transplantation. To investigate whether urine metabolites predict kidney allograft status, we determined levels of 749 metabolites in 1516 urine samples from 241 kidney graft recipients enrolled in the prospective multicenter Clinical Trials in Organ Transplantation-04 study. A metabolite signature of the ratio of 3-sialyllactose to xanthosine in biopsy specimen-matched urine supernatants best discriminated acute cellular rejection biopsy specimens from specimens without rejection. For clinical application, we developed a highthroughput mass spectrometry-based assay that enabled absolute and rapid quantification of the 3-sialyllactose-to-xanthosine ratio in urine samples. A composite signature of ratios of 3-sialyllactose to xanthosine and quinolinate to X-16397 and our previously reported urinary cell mRNA signature of 18S ribosomal RNA, CD3« mRNA, and interferon-inducible protein-10 mRNA outperformed the metabolite signatures and the mRNA signature. The area under the receiver operating characteristics curve for the composite metabolitemRNA signature was 0.93, and the signature was diagnostic of acute cellular rejection with a specificity of 84% and a sensitivity of 90%. The composite signature, developed using solely biopsy specimen-matched urine samples, predicted future acute cellular rejection when applied to pristine samples taken days to weeks before biopsy. We conclude that metabolite profiling of urine offers a noninvasive means of diagnosing and prognosticating acute cellular rejection in the human kidney allograft, and that the combined metabolite and mRNA signature is diagnostic and prognostic of acute cellular rejection with very high accuracy.

show abstract

Sialyllactose in Viral Membrane Gangliosides Is a Novel Molecular Recognition Pattern for Mature Dendritic Cell Capture of HIV-1

Abstract: An accessible sialyllactose moiety on viral membrane gangliosides is shown to be essential for HIV-1 uptake into mature dendritic cells, thereby promoting viral transfer and infection of bystander CD4+ T lymphocytes.

Cited by 76 publications

References 73 publications

Cell-Free versus Cell-to-Cell Infection by Human Immunodeficiency Virus Type 1 and Human T-Lymphotropic Virus Type 1: Exploring the Link among Viral Source, Viral Trafficking, and Viral Replication

Cell-Free versus Cell-to-Cell Infection by Human Immunodeficiency Virus Type 1 and Human T-Lymphotropic Virus Type 1: Exploring the Link among Viral Source, Viral Trafficking, and Viral Replication

Virus Particle Release from Glycosphingolipid-Enriched Microdomains Is Essential for Dendritic Cell-Mediated Capture and Transfer of HIV-1 and Henipavirus

Urine Metabolite Profiles Predictive of Human Kidney Allograft Status

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