Endothelial Galectin-1 Binds to Specific Glycans on Nipah Virus Fusion Protein and Inhibits Maturation, Mobility, and Function to Block Syncytia Formation
Nipah virus targets human endothelial cells via NiV-F and NiV-G envelope glycoproteins, resulting in endothelial syncytia formation and vascular compromise. Endothelial cells respond to viral infection by releasing innate immune effectors, including galectins, which are secreted proteins that bind to specific glycan ligands on cell surface glycoproteins. We demonstrate that galectin-1 reduces NiV-F mediated fusion of endothelial cells, and that endogenous galectin-1 in endothelial cells is sufficient to inhibit syncytia formation. Galectin-1 regulates NiV-F mediated cell fusion at three distinct points, including retarding maturation of nascent NiV-F, reducing NiV-F lateral mobility on the plasma membrane, and directly inhibiting the conformational change in NiV-F required for triggering fusion. Characterization of the NiV-F N-glycome showed that the critical site for galectin-1 inhibition is rich in glycan structures known to bind galectin-1. These studies identify a unique set of mechanisms for regulating pathophysiology of NiV infection at the level of the target cell.
Vyšlo v časopise:
Endothelial Galectin-1 Binds to Specific Glycans on Nipah Virus Fusion Protein and Inhibits Maturation, Mobility, and Function to Block Syncytia Formation. PLoS Pathog 6(7): e32767. doi:10.1371/journal.ppat.1000993
Kategorie:
Research Article
prolekare.web.journal.doi_sk:
https://doi.org/10.1371/journal.ppat.1000993
Souhrn
Nipah virus targets human endothelial cells via NiV-F and NiV-G envelope glycoproteins, resulting in endothelial syncytia formation and vascular compromise. Endothelial cells respond to viral infection by releasing innate immune effectors, including galectins, which are secreted proteins that bind to specific glycan ligands on cell surface glycoproteins. We demonstrate that galectin-1 reduces NiV-F mediated fusion of endothelial cells, and that endogenous galectin-1 in endothelial cells is sufficient to inhibit syncytia formation. Galectin-1 regulates NiV-F mediated cell fusion at three distinct points, including retarding maturation of nascent NiV-F, reducing NiV-F lateral mobility on the plasma membrane, and directly inhibiting the conformational change in NiV-F required for triggering fusion. Characterization of the NiV-F N-glycome showed that the critical site for galectin-1 inhibition is rich in glycan structures known to bind galectin-1. These studies identify a unique set of mechanisms for regulating pathophysiology of NiV infection at the level of the target cell.
Zdroje
1. BlumLS
KhanR
NaharN
BreimanRF
2009 In-depth assessment of an outbreak of Nipah encephalitis with person-to-person transmission in Bangladesh: implications for prevention and control strategies. Am J Trop Med Hyg 80 96 102
2. WongKT
ShiehWJ
KumarS
NorainK
AbdullahW
2002 Nipah virus infection: pathology and pathogenesis of an emerging paramyxoviral zoonosis. Am J Pathol 161 2153 2167
3. HooperP
ZakiS
DanielsP
MiddletonD
2001 Comparative pathology of the diseases caused by Hendra and Nipah viruses. Microbes Infect 3 315 322
4. MaisnerA
NeufeldJ
WeingartlH
2009 Organ- and endotheliotropism of Nipah virus infections in vivo and in vitro. Thromb Haemost 102 1014 1023
5. EatonBT
BroderCC
MiddletonD
WangLF
2006 Hendra and Nipah viruses: different and dangerous. Nat Rev Microbiol 4 23 35
6. NegreteOA
LevroneyEL
AguilarHC
Bertolotti-CiarletA
NazarianR
2005 EphrinB2 is the entry receptor for Nipah virus, an emergent deadly paramyxovirus. Nature 436 401 405
7. BonaparteMI
DimitrovAS
BossartKN
CrameriG
MungallBA
2005 Ephrin-B2 ligand is a functional receptor for Hendra virus and Nipah virus. Proc Natl Acad Sci U S A 102 10652 10657
8. NegreteOA
WolfMC
AguilarHC
EnterleinS
WangW
2006 Two key residues in ephrinB3 are critical for its use as an alternative receptor for Nipah virus. PLoS Pathog 2 e7
9. LeeB
2007 Envelope-receptor interactions in Nipah virus pathobiology. Ann N Y Acad Sci 1102 51 65
10. VogtC
EickmannM
DiederichS
MollM
MaisnerA
2005 Endocytosis of the Nipah virus glycoproteins. J Virol 79 3865 3872
11. DiederichS
MollM
KlenkHD
MaisnerA
2005 The nipah virus fusion protein is cleaved within the endosomal compartment. J Biol Chem 280 29899 29903
12. PagerCT
CraftWWJr
PatchJ
DutchRE
2006 A mature and fusogenic form of the Nipah virus fusion protein requires proteolytic processing by cathepsin L. Virology 346 251 257
13. AguilarHC
MatreyekKA
FiloneCM
HashimiST
LevroneyEL
2006 N-glycans on Nipah virus fusion protein protect against neutralization but reduce membrane fusion and viral entry. J Virol 80 4878 4889
14. MollM
KaufmannA
MaisnerA
2004 Influence of N-glycans on processing and biological activity of the nipah virus fusion protein. J Virol 78 7274 7278
15. RabinovichGA
BaumLG
TinariN
PaganelliR
NatoliC
2002 Galectins and their ligands: amplifiers, silencers or tuners of the inflammatory response? Trends Immunol 23 313 320
16. WarkeRV
XhajaK
MartinKJ
FournierMF
ShawSK
2003 Dengue virus induces novel changes in gene expression of human umbilical vein endothelial cells. J Virol 77 11822 11832
17. RamasamyS
DuraisamyS
BarbashovS
KawanoT
KharbandaS
2007 The MUC1 and galectin-3 oncoproteins function in a microRNA-dependent regulatory loop. Mol Cell 27 992 1004
18. BaumLG
SeilhamerJJ
PangM
LevineWB
BeynonD
1995 Synthesis of an endogeneous lectin, galectin-1, by human endothelial cells is up-regulated by endothelial cell activation. Glycoconj J 12 63 68
19. HeJ
BaumLG
2006 Endothelial cell expression of galectin-1 induced by prostate cancer cells inhibits T-cell transendothelial migration. Lab Invest 86 578 590
20. LevroneyEL
AguilarHC
FulcherJA
KohatsuL
PaceKE
2005 Novel innate immune functions for galectin-1: galectin-1 inhibits cell fusion by Nipah virus envelope glycoproteins and augments dendritic cell secretion of proinflammatory cytokines. J Immunol 175 413 420
21. ThijssenVL
HulsmansS
GriffioenAW
2008 The galectin profile of the endothelium: altered expression and localization in activated and tumor endothelial cells. Am J Pathol 172 545 553
22. GarnerOB
BaumLG
2008 Galectin-glycan lattices regulate cell-surface glycoprotein organization and signalling. Biochem Soc Trans 36 1472 1477
23. AguilarHC
AtamanZA
AspericuetaV
FangAQ
StroudM
2009 A novel receptor-induced activation site in the Nipah virus attachment glycoprotein (G) involved in triggering the fusion glycoprotein (F). J Biol Chem 284 1628 1635
24. LajoieP
PartridgeEA
GuayG
GoetzJG
PawlingJ
2007 Plasma membrane domain organization regulates EGFR signaling in tumor cells. J Cell Biol 179 341 356
25. OhtsuboK
TakamatsuS
MinowaMT
YoshidaA
TakeuchiM
2005 Dietary and genetic control of glucose transporter 2 glycosylation promotes insulin secretion in suppressing diabetes. Cell 123 1307 1321
26. AbbottKL
MatthewsRT
PierceM
2008 Receptor tyrosine phosphatase beta (RPTPbeta) activity and signaling are attenuated by glycosylation and subsequent cell surface galectin-1 binding. J Biol Chem 283 33026 33035
27. DiederichS
ThielL
MaisnerA
2008 Role of endocytosis and cathepsin-mediated activation in Nipah virus entry. Virology 375 391 400
28. AguilarHC
MatreyekKA
ChoiDY
FiloneCM
YoungS
2007 Polybasic KKR motif in the cytoplasmic tail of Nipah virus fusion protein modulates membrane fusion by inside-out signaling. J Virol 81 4520 4532
29. LambRA
JardetzkyTS
2007 Structural basis of viral invasion: lessons from paramyxovirus F. Curr Opin Struct Biol 17 427 436
30. KohatsuL
HsuDK
JegalianAG
LiuFT
BaumLG
2006 Galectin-3 induces death of Candida species expressing specific beta-1,2-linked mannans. J Immunol 177 4718 4726
31. StowellSR
ArthurCM
Dias-BaruffiM
RodriguesLC
GourdineJP
Innate immune lectins kill bacteria expressing blood group antigen. Nat Med
32. MoodyTN
OchiengJ
VillaltaF
2000 Novel mechanism that Trypanosoma cruzi uses to adhere to the extracellular matrix mediated by human galectin-3. FEBS Lett 470 305 308
33. OuelletM
MercierS
PelletierI
BounouS
RoyJ
2005 Galectin-1 acts as a soluble host factor that promotes HIV-1 infectivity through stabilization of virus attachment to host cells. J Immunol 174 4120 4126
34. FowlerM
ThomasRJ
AthertonJ
RobertsIS
HighNJ
2006 Galectin-3 binds to Helicobacter pylori O-antigen: it is upregulated and rapidly secreted by gastric epithelial cells in response to H. pylori adhesion. Cell Microbiol 8 44 54
35. MercierS
St-PierreC
PelletierI
OuelletM
TremblayMJ
2008 Galectin-1 promotes HIV-1 infectivity in macrophages through stabilization of viral adsorption. Virology 371 121 129
36. OkumuraCY
BaumLG
JohnsonPJ
2008 Galectin-1 on cervical epithelial cells is a receptor for the sexually transmitted human parasite Trichomonas vaginalis. Cell Microbiol 10 2078 2090
37. GauthierS
PelletierI
OuelletM
VargasA
TremblayMJ
2008 Induction of galectin-1 expression by HTLV-I Tax and its impact on HTLV-I infectivity. Retrovirology 5 105
38. VastaGR
2009 Roles of galectins in infection. Nat Rev Microbiol 7 424 438
39. SatoS
St-PierreC
BhaumikP
NieminenJ
2009 Galectins in innate immunity: dual functions of host soluble beta-galactoside-binding lectins as damage-associated molecular patterns (DAMPs) and as receptors for pathogen-associated molecular patterns (PAMPs). Immunol Rev 230 172 187
40. Pais-CorreiaAM
SachseM
GuadagniniS
RobbiatiV
LasserreR
Biofilm-like extracellular viral assemblies mediate HTLV-1 cell-to-cell transmission at virological synapses. Nat Med 16 83 89
41. BrewerCF
MiceliMC
BaumLG
2002 Clusters, bundles, arrays and lattices: novel mechanisms for lectin-saccharide-mediated cellular interactions. Curr Opin Struct Biol 12 616 623
42. BracciaA
VillaniM
ImmerdalL
Niels-ChristiansenLL
NystromBT
2003 Microvillar membrane microdomains exist at physiological temperature. Role of galectin-4 as lipid raft stabilizer revealed by “superrafts”. J Biol Chem 278 15679 15684
43. NguyenJT
EvansDP
GalvanM
PaceKE
LeitenbergD
2001 CD45 modulates galectin-1-induced T cell death: regulation by expression of core 2 O-glycans. J Immunol 167 5697 5707
44. LiuSD
TomassianT
BruhnKW
MillerJF
PoirierF
2009 Galectin-1 tunes TCR binding and signal transduction to regulate CD8 burst size. J Immunol 182 5283 5295
45. LauKS
PartridgeEA
GrigorianA
SilvescuCI
ReinholdVN
2007 Complex N-glycan number and degree of branching cooperate to regulate cell proliferation and differentiation. Cell 129 123 134
46. StowellSR
ArthurCM
MehtaP
SlaninaKA
BlixtO
2008 Galectin-1, -2, and -3 exhibit differential recognition of sialylated glycans and blood group antigens. J Biol Chem 283 10109 10123
47. TanakaH
ChibaH
InokoshiJ
KunoA
SugaiT
2009 Mechanism by which the lectin actinohivin blocks HIV infection of target cells. Proc Natl Acad Sci U S A
48. MenonS
RosenbergK
GrahamSA
WardEM
TaylorME
2009 Binding-site geometry and flexibility in DC-SIGN demonstrated with surface force measurements. Proc Natl Acad Sci U S A 106 11524 11529
49. DamTK
BrewerCF
2009 Lectins as Pattern Recognition Molecules: The Effects of Epitope Density in Innate Immunity#. Glycobiology
50. LiY
ClevelandB
KlotsI
TravisB
RichardsonBA
2008 Removal of a single N-linked glycan in human immunodeficiency virus type 1 gp120 results in an enhanced ability to induce neutralizing antibody responses. J Virol 82 638 651
51. IidaA
OzakiK
TanakaT
NakamuraY
2005 Fine-scale SNP map of an 11-kb genomic region at 22q13.1 containing the galectin-1 gene. J Hum Genet 50 42 45
52. OzakiK
InoueK
SatoH
IidaA
OhnishiY
2004 Functional variation in LGALS2 confers risk of myocardial infarction and regulates lymphotoxin-alpha secretion in vitro. Nature 429 72 75
53. PaceKE
LeeC
StewartPL
BaumLG
1999 Restricted receptor segregation into membrane microdomains occurs on human T cells during apoptosis induced by galectin-1. J Immunol 163 3801 3811
54. BiS
EarlLA
JacobsL
BaumLG
2008 Structural features of galectin-9 and galectin-1 that determine distinct T cell death pathways. J Biol Chem 283 12248 12258
55. LinebergerJE
DanzeisenR
HazudaDJ
SimonAJ
MillerMD
2002 Altering expression levels of human immunodeficiency virus type 1 gp120-gp41 affects efficiency but not kinetics of cell-cell fusion. J Virol 76 3522 3533
56. ReevesJD
MiamidianJL
BisconeMJ
LeeFH
AhmadN
2004 Impact of mutations in the coreceptor binding site on human immunodeficiency virus type 1 fusion, infection, and entry inhibitor sensitivity. J Virol 78 5476 5485
57. DoucetN
De WalsPY
PelletierJN
2004 Site-saturation mutagenesis of Tyr-105 reveals its importance in substrate stabilization and discrimination in TEM-1 beta-lactamase. J Biol Chem 279 46295 46303
58. WolfMC
WangY
FreibergAN
AguilarHC
HolbrookMR
2009 A catalytically and genetically optimized beta-lactamase-matrix based assay for sensitive, specific, and higher throughput analysis of native henipavirus entry characteristics. Virol J 6 119
59. Jang-LeeJ
NorthSJ
Sutton-SmithM
GoldbergD
PanicoM
2006 Glycomic profiling of cells and tissues by mass spectrometry: fingerprinting and sequencing methodologies. Methods Enzymol 415 59 86
60. PangPC
TissotB
DrobnisEZ
MorrisHR
DellA
2009 Analysis of the human seminal plasma glycome reveals the presence of immunomodulatory carbohydrate functional groups. J Proteome Res 8 4906 4915
61. TissotB
NorthSJ
CeroniA
PangPC
PanicoM
2009 Glycoproteomics: past, present and future. FEBS Lett 583 1728 1735
62. GoldbergD
BernM
ParryS
Sutton-SmithM
PanicoM
2007 Automated N-glycopeptide identification using a combination of single- and tandem-MS. J Proteome Res 6 3995 4005
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Hygiena a epidemiológia Infekčné lekárstvo LaboratóriumČlánok vyšiel v časopise
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