Host-Soluble Galectin-1 Promotes HIV-1 Replication through a Direct Interaction with Glycans of Viral gp120 and Host CD4

St-Pierre, C.; Manya, Hiroshi; Ouellet, Michel; Clark, Gary F.; Endo, Tamao; Tremblay, Michel J.; Sato, Sachiko

doi:10.1128/jvi.05351-11

Cited by 88 publications

(122 citation statements)

References 64 publications

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“…In its normal function, galectin-1 binds to glycans on the CD4 coreceptor of T cells to prevent autorecognition. However, when HIV is present, the galectin bridges the CD4 coreceptor and gp120 ligands, thus facilitating HIV infection of the T cell (149). There might also be a link between galectins and EV attachment.…”

Section: Shared Receptors For Virus and Ev Entry Lectinsmentioning

confidence: 99%

Extracellular Vesicles Exploit Viral Entry Routes for Cargo Delivery

Dongen

Masoumi

Witwer

et al. 2016

Microbiol Mol Biol Rev

219

184

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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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Section: Shared Receptors For Virus and Ev Entry Lectinsmentioning

confidence: 99%

Extracellular Vesicles Exploit Viral Entry Routes for Cargo Delivery

Dongen

Masoumi

Witwer

et al. 2016

Microbiol Mol Biol Rev

219

184

View full text Add to dashboard Cite

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“…Galectin-1 stabilizes HIV-1 attachment and adsorption to host cells by binding specifically to clustered complex N-glycans on gp120 and CD4, bridging the virus to the target cell (20)(21)(22). We sought to determine whether complex N-glycans that bear glycan ligands recognized by galectin-1 were involved in the galectin-1-mediated increase in viral entry of NiVpp.…”

Section: Galectin-1 Increases Viral Infection Of Endothelial Cellsmentioning

confidence: 99%

“…In contrast, Pseudomonas aeruginosa and Trypanosoma cruzi use galectin-3 to bind to and infect human cells, and galectin-1 on human cervical epithelial cells is an attachment factor for Trichomonas vaginalis (17)(18)(19). Similarly, galectin-1, which preferentially recognizes LacNAc (Gal␤1,4GlcNAc)-containing glycans, increases human immunodeficiency virus (HIV) infection of monocytederived macrophages through stabilization of virus attachment (20)(21)(22), and galectin-9 promotes HIV infection of T cells by regulating the cell surface redox status (23). Thus, different galectins can have pleiotropic and sometimes opposing roles in the etiology and pathophysiology of microbial infections.…”

mentioning

confidence: 99%

Timing of Galectin-1 Exposure Differentially Modulates Nipah Virus Entry and Syncytium Formation in Endothelial Cells

Garner

Yun

Pernet

et al. 2015

J Virol

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Nipah virus (NiV) is a deadly emerging enveloped paramyxovirus that primarily targets human endothelial cells. Endothelial cells express the innate immune effector galectin-1 that we have previously shown can bind to specific N-glycans on the NiV envelope fusion glycoprotein (F). NiV-F mediates fusion of infected endothelial cells into syncytia, resulting in endothelial disruption and hemorrhage. Galectin-1 is an endogenous carbohydrate-binding protein that binds to specific glycans on NiV-F to reduce endothelial cell fusion, an effect that may reduce pathophysiologic sequelae of NiV infection. However, galectins play multiple roles in regulating host-pathogen interactions; for example, galectins can promote attachment of HIV to T cells and macrophages and attachment of HSV-1 to keratinocytes but can also inhibit influenza entry into airway epithelial cells. Using live Nipah virus, in the present study, we demonstrate that galectin-1 can enhance NiV attachment to and infection of primary human endothelial cells by bridging glycans on the viral envelope to host cell glycoproteins. In order to exhibit an enhancing effect, galectin-1 must be present during the initial phase of virus attachment; in contrast, addition of galectin-1 postinfection results in reduced production of progeny virus and syncytium formation. Thus, galectin-1 can have dual and opposing effects on NiV infection of human endothelial cells. While various roles for galectin family members in microbial-host interactions have been described, we report opposing effects of the same galectin family member on a specific virus, with the timing of exposure during the viral life cycle determining the outcome. IMPORTANCENipah virus is an emerging pathogen that targets endothelial cells lining blood vessels; the high mortality rate (up to 70%) in Nipah virus infections results from destruction of these cells and resulting catastrophic hemorrhage. Host factors that promote or prevent Nipah virus infection are not well understood. Endogenous human lectins, such as galectin-1, can function as pattern recognition receptors to reduce infection and initiate immune responses; however, lectins can also be exploited by microbes to enhance infection of host cells. We found that galectin-1, which is made by inflamed endothelial cells, can both promote Nipah virus infection of endothelial cells by "bridging" the virus to the cell, as well as reduce production of progeny virus and reduce endothelial cell fusion and damage, depending on timing of galectin-1 exposure. This is the first report of spatiotemporal opposing effects of a host lectin for a virus in one type of host cell. N ipah virus (NiV) is an emerging zoonotic paramyxovirus that targets endothelial and neural cells. Infection with NiV can result in a severe encephalitic or respiratory syndrome with case fatality rates ranging from 40 to 100% in humans (1, 2). Although initial outbreaks involved transmission from bats to pigs and then from pigs to humans, more recent outbreaks have been shown to involve...

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“…For example, clustering of complex-type glycans on the HIV coat protein GP120 in its native conformation imparts structural constraints that prevent galectin-3 binding, yet permit galectin-1 binding. 73,101 Thus, synthetic glycoclusters with fine control of glycan chemistry and physical display may provide new opportunities for creating more robust galectin inhibitors. Toward this end, we have recently developed a synthetic glycopeptide, GlcNAc-QQKFQFQFEQQ (GlcNAc-Q11), which self-assembles into b-sheet nanofibers under aqueous conditions to provide highly multivalent glycoclusters 101 ( Figure 4).…”

Section: Inhibiting Galectin-t-cell Interactions To Maintain or Restomentioning

confidence: 99%

Engineering galectin–glycan interactions for immunotherapy and immunomodulation

Farhadi

Hudalla

2016

Exp Biol Med (Maywood)

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Galectins, a 15-member family of soluble carbohydrate-binding proteins, are receiving increasing interest as therapeutic targets for immunotherapy and immunomodulation due to their role as extracellular signals that regulate innate and adaptive immune cell phenotype and function. However, different galectins can have redundant, synergistic, or antagonistic signaling activity in normal immunological responses, such as resolution of inflammation and induction of antigen-specific tolerance. In addition, certain galectins can be hijacked to promote progression of immunopathologies, such as tumor immune privilege, metastasis, and viral infection, while others can inhibit these processes. Thus, eliciting a desired immunological outcome will likely necessitate therapeutics that can precisely enhance or inhibit particular galectin-glycan interactions. Multivalency is an important determinant of the affinity and specificity of natural galectin-glycan interactions, and is emerging as a key design element for therapeutics that can effectively manipulate galectin bioactivity. This minireview surveys current molecular and biomaterial engineering approaches to create therapeutics that can stabilize galectin multivalency or recapitulate natural glycan multivalency (i.e. ''the glycocluster effect''). In particular, we highlight examples of using natural and engineered multivalent galectins for immunosuppression and immune tolerance, with a particular emphasis on treating autoimmune diseases or avoiding transplant rejection. In addition, we present examples of multivalent inhibitors of galectin-glycan interactions to maintain or restore T-cell function, with a particular emphasis on promoting antitumor immunity. Finally, we discuss emerging opportunities to further engineer galectin-glycan interactions for immunotherapy and immunomodulation.

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Host-Soluble Galectin-1 Promotes HIV-1 Replication through a Direct Interaction with Glycans of Viral gp120 and Host CD4

Cited by 88 publications

References 64 publications

Extracellular Vesicles Exploit Viral Entry Routes for Cargo Delivery

Extracellular Vesicles Exploit Viral Entry Routes for Cargo Delivery

Timing of Galectin-1 Exposure Differentially Modulates Nipah Virus Entry and Syncytium Formation in Endothelial Cells

Engineering galectin–glycan interactions for immunotherapy and immunomodulation

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