Galectin-1 Binds to Influenza Virus and Ameliorates Influenza Virus Pathogenesis

Yang, Mei; Chen, Yu-Hung; Wang, Shainn Wei; Huang, Yen Jang; Leu, Chia Hsing; Yeh, Nai Chi; Chu, Chun Yen; Lin, Chia Cheng; Shieh, Gia Shing; Chen, Yuh Ling; Wang, Jen Ren; Wang, Ching Ho; Wu, Chao‐Liang; Shiau, Ai‐Li

doi:10.1128/jvi.00301-11

Cited by 111 publications

(135 citation statements)

References 56 publications

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“…Galectin-1 bound to influenza virus reduced virus entry into host cells; moreover, intranasal administration of galectin-1 enhanced survival of mice infected with a lethal dose of influenza virus, and galectin-1-null mice were more susceptible to influenza virus infection than were wild-type mice (39). In contrast, galectin-1 increased HIV-1 infection of monocyte-derived macrophages through stabilization of virus attachment and adsorption (20,21).…”

Section: Discussionmentioning

confidence: 82%

“…Although other lectins have been shown to have effects both beneficial and detrimental to the host in microbial infections (20,21,36,39), we report these opposing effects for a single virus, NiV, and a single lectin, galectin-1, in the same host cell. These findings may help to explain the range of clinical outcomes of NiV infection, since some patients recover fully after infection, while other patients succumb.…”

Section: Discussionmentioning

confidence: 89%

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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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Section: Discussionmentioning

confidence: 82%

Section: Discussionmentioning

confidence: 89%

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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“…Thus, CvGal1 would function as a key component of the innate immune defense [27, 57]. The protective role of mammalian galectins against viral and bacterial infection has been reported in recent years [91–93]. The oyster galectin CvGal1 also selectively and specifically recognizes microalgal species such as Tetraselmis spp, an abundant phytoplankton component in the oyster’s diet internalized by filter-feeding, suggesting that CvGal1 is also involved in selective phagocytosis and intracellular digestion of the microalgal food [27, 57] (Fig 6.A).…”

Section: Galectins In Aquatic Mollusksmentioning

confidence: 99%

“…Furthermore, galectin-1 also mediates the attachment of Trichomonas vaginalis , an obligate extracellular parasite, to the cervix epithelium [104, 105]. These observations are in sharp contrast with the protective role of the same galectin-1 during infections by influenza A virus [93] and Dengue virus [92]. Therefore, these examples further support the notion that although galectins may participate as PRRs in innate immune recognition by both invertebrates and vertebrates, including man, some viral and bacterial pathogens and parasites have co-evolved with their host to subvert the defensive role of galectins to gain entry into the host internal milieu [27].…”

Section: Galectins In Aquatic Mollusksmentioning

confidence: 99%

Structural, functional, and evolutionary aspects of galectins in aquatic mollusks: From a sweet tooth to the Trojan horse

Vasta

Feng

Bianchet

et al. 2015

Fish & Shellfish Immunology

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Galectins constitute a conserved and widely distributed lectin family characterized by their binding affinity for β-galactosides and a unique binding site sequence motif in the carbohydrate recognition domain (CRD). In spite of their structural conservation, galectins display a remarkable functional diversity, by participating in developmental processes, cell adhesion and motility, regulation of immune homeostasis, and recognition of glycans on the surface of viruses, bacteria and protozoan parasites. In contrast with mammals, and other vertebrate and invertebrate taxa, the identification and characterization of bona fide galectins in aquatic mollusks has been relatively recent. Most of the studies have focused on the identification and domain organization of galectin-like transcripts or proteins in diverse tissues and cell types, including hemocytes, and their expression upon environmental or infectious challenge. Lectins from the eastern oyster Crassostrea virginica, however, have been characterized in their molecular, structural and functional aspects and some notable features have become apparent in the galectin repertoire of aquatic mollusks. These including less diversified galectin repertoires and different domain organizations relative to those observed in vertebrates, carbohydrate specificity for blood group oligosaccharides, and up regulation of galectin expression by infectious challenge, a feature that supports their proposed role(s) in innate immune responses. Although galectins from some aquatic mollusks have been shown to recognize microbial pathogens and parasites and promote their phagocytosis, they can also selectively bind to phytoplankton components, suggesting that they also participate in uptake and intracellular digestion of microalgae. In addition, the experimental evidence suggests that the protozoan parasite Perkinsus marinus has co-evolved with the oyster host to be selectively recognized by the oyster hemocyte galectins over algal food or bacterial pathogens, thereby subverting the oyster’s innate immune/feeding recognition mechanisms to gain entry into the host cells.

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“…Key sequential steps in viral pathogenesis at a cellular level are receptor mediated endocytosis, uncoating, nuclear transcription of viral mRNAs, synthesis of viral proteins in the cytoplasm, viral nucleocapsid assembly in the nucleus, followed by their transport to the plasma membrane where budding and release of new virions through the action of the NA molecule, the second key surface expressed viral protein takes place. 4,[18][19][20] Release of the virus from the cell is associated with cell lysis. 4 The host immune response to influenza virus infection involves both innate and adaptive mechanisms.…”

Section: Disease Pathogenesis and Host Responsementioning

confidence: 99%

Evaluating the case for trivalent or quadrivalent influenza vaccines

Baxter

2016

Human Vaccines & Immunotherapeutics

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Influenza viruses circulate widely throughout the world and it is estimated that they affect between 5 and 15% of the population annually. Since 1977, four viruses co-circulate -two A Viruses (H1N1 and H3N2) and two B viruses (B Yamagata and B Victoria). Type A viruses generally cause up to two thirds of annual infections, although single country studies have shown that B infections may be the predominant virus in the one year in four.Influenza vaccines have traditionally included the hamagglutinins and neuraminidases from the two circulating A viruses and either B Yamagata or B Victoria -however, selecting the B strain for inclusion in these trivalent vaccines has variable success. The alternative approach is to include both B strains in a quadrivalent vaccine. Immunological studies of such vaccines show non-inferiority with a trivalent vaccine comparator, and significant superiority to the additional B strain.Quadrivalent vaccines are more expensive than trivalent preparations but theoretical evidence would suggest they are likely to be more effective and therefore play a much greater role in national immunisation programmes in the future.

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Galectin-1 Binds to Influenza Virus and Ameliorates Influenza Virus Pathogenesis

Cited by 111 publications

References 56 publications

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

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

Structural, functional, and evolutionary aspects of galectins in aquatic mollusks: From a sweet tooth to the Trojan horse

Evaluating the case for trivalent or quadrivalent influenza vaccines

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