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Tyrosine Sulfation of the Amino Terminus of PSGL-1 Is Critical for Enterovirus 71 Infection


Enterovirus 71 (EV71) is one of the major causative agents of hand, foot, and mouth disease, a common febrile disease in children; however, EV71 has been also associated with various neurological diseases including fatal cases in large EV71 outbreaks particularly in the Asia Pacific region. Recently we identified human P-selectin glycoprotein ligand-1 (PSGL-1) as a cellular receptor for entry and replication of EV71 in leukocytes. PSGL-1 is a sialomucin expressed on the surface of leukocytes, serves as a high affinity counterreceptor for selectins, and mediates leukocyte rolling on the endothelium. The PSGL-1–P-selectin interaction requires sulfation of at least one of three clustered tyrosines and an adjacent O-glycan expressing sialyl Lewis x in an N-terminal region of PSGL-1. To elucidate the molecular basis of the PSGL-1–EV71 interaction, we generated a series of PSGL-1 mutants and identified the post-translational modifications that are critical for binding of PSGL-1 to EV71. We expressed the PSGL-1 mutants in 293T cells and the transfected cells were assayed for their abilities to bind to EV71 by flow cytometry. We found that O-glycosylation on T57, which is critical for PSGL-1–selectin interaction, is not necessary for PSGL-1 binding to EV71. On the other hand, site-directed mutagenesis at one or more potential tyrosine sulfation sites in the N-terminal region of PSGL-1 significantly impaired PSGL-1 binding to EV71. Furthermore, an inhibitor of sulfation, sodium chlorate, blocked the PSGL-1–EV71 interaction and inhibited PSGL-1-mediated viral replication of EV71 in Jurkat T cells in a dose-dependent manner. Thus, the results presented in this study reveal that tyrosine sulfation, but not O-glycosylation, in the N-terminal region of PSGL-1 may facilitate virus entry and replication of EV71 in leukocytes.


Vyšlo v časopise: Tyrosine Sulfation of the Amino Terminus of PSGL-1 Is Critical for Enterovirus 71 Infection. PLoS Pathog 6(11): e32767. doi:10.1371/journal.ppat.1001174
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1001174

Souhrn

Enterovirus 71 (EV71) is one of the major causative agents of hand, foot, and mouth disease, a common febrile disease in children; however, EV71 has been also associated with various neurological diseases including fatal cases in large EV71 outbreaks particularly in the Asia Pacific region. Recently we identified human P-selectin glycoprotein ligand-1 (PSGL-1) as a cellular receptor for entry and replication of EV71 in leukocytes. PSGL-1 is a sialomucin expressed on the surface of leukocytes, serves as a high affinity counterreceptor for selectins, and mediates leukocyte rolling on the endothelium. The PSGL-1–P-selectin interaction requires sulfation of at least one of three clustered tyrosines and an adjacent O-glycan expressing sialyl Lewis x in an N-terminal region of PSGL-1. To elucidate the molecular basis of the PSGL-1–EV71 interaction, we generated a series of PSGL-1 mutants and identified the post-translational modifications that are critical for binding of PSGL-1 to EV71. We expressed the PSGL-1 mutants in 293T cells and the transfected cells were assayed for their abilities to bind to EV71 by flow cytometry. We found that O-glycosylation on T57, which is critical for PSGL-1–selectin interaction, is not necessary for PSGL-1 binding to EV71. On the other hand, site-directed mutagenesis at one or more potential tyrosine sulfation sites in the N-terminal region of PSGL-1 significantly impaired PSGL-1 binding to EV71. Furthermore, an inhibitor of sulfation, sodium chlorate, blocked the PSGL-1–EV71 interaction and inhibited PSGL-1-mediated viral replication of EV71 in Jurkat T cells in a dose-dependent manner. Thus, the results presented in this study reveal that tyrosine sulfation, but not O-glycosylation, in the N-terminal region of PSGL-1 may facilitate virus entry and replication of EV71 in leukocytes.


Zdroje

1. AlexanderJPJr

BadenL

PallanschMA

AndersonLJ

1994 Enterovirus 71 infections and neurologic disease–United States, 1977–1991. J Infect Dis 169 905 908

2. McMinnPC

2002 An overview of the evolution of enterovirus 71 and its clinical and public health significance. FEMS Microbiol Rev 26 91 107

3. BibleJM

PantelidisP

ChanPKS

TongCYW

2007 Genetic evolution of enterovirus 71: epidemiological and pathological implications. Rev Med Virol 17 371 379

4. YangF

RenL

XiongZ

LiJ

XiaoY

2009 Enterovirus 71 outbreak in the People's Republic of China in 2008. J Clin Microbiol 47 2351 2352

5. NishimuraY

ShimojimaM

TanoY

MiyamuraT

WakitaT

2009 Human P-selectin glycoprotein ligand-1 is a functional receptor for enterovirus 71. Nat Med 15 794 797

6. YamayoshiS

YamashitaY

LiJ

HanagataN

MinowaT

2009 Scavenger receptor B2 is a cellular receptor for enterovirus 71. Nat Med 15 798 801

7. EskelinenEL

TanakaY

SaftigP

2003 At the acidic edge: emerging functions for lysosomal membrane proteins. Trends Cell Biol 13 137 145

8. LaszikZ

JansenPJ

CummingsRD

TedderTF

McEverRP

1996 P-selectin glycoprotein ligand-1 is broadly expressed in cells of myeloid, lymphoid, and dendritic lineage and in some nonhematopoietic cells. Blood 88 3010 3021

9. HirataT

FurukawaY

YangBG

HieshimaK

FukudaM

2004 Human P-selectin glycoprotein ligand-1 (PSGL-1) interacts with the skin-associated chemokine CCL27 via sulfated tyrosines at the PSGL-1 amino terminus. J Biol Chem 279 51775 51782

10. SakoD

ChangXJ

BaroneKM

VachinoG

WhiteHM

1993 Expression cloning of a functional glycoprotein ligand for P-selectin. Cell 75 1179 1186

11. SomersWS

TangJ

ShawGD

CamphausenRT

2000 Insights into the molecular basis of leukocyte tethering and rolling revealed by structures of P- and E-selectin bound to SLeX and PSGL-1. Cell 103 467 479

12. LiuWJ

RamachandranV

KangJ

KishimotoTK

CummingsRD

1998 Identification of N-terminal residues on P-selectin glycoprotein ligand-1 required for binding to P-selectin. J Biol Chem 273 7078 7087

13. PouyaniT

SeedB

1995 PSGL-1 recognition of P-selectin is controlled by a tyrosine sulfation consensus at the PSGL-1 amino terminus. Cell 83 333 343

14. SakoD

ComessKM

BaroneKM

CamphausenRT

CummingDA

1995 A sulfated peptide segment at the amino terminus of PSGL-1 is critical for P-selectin binding. Cell 83 323 331

15. WilkinsPP

MooreKL

McEverRP

CummingsRD

1995 Tyrosine sulfation of P-selectin glycoprotein ligand-1 is required for high affinity binding to P-selectin. J Biol Chem 270 22677 22680

16. KehoeJW

BertozziCR

2000 Tyrosine sulfation: a modulator of extracellular protein-protein interactions. Chem Biol 7 R57 61

17. MooreKL

2003 The biology and enzymology of protein tyrosine O-sulfation. J Biol Chem 278 24243 24246

18. FarzanM

MirzabekovT

KolchinskyP

WyattR

CayabyabM

1999 Tyrosine sulfation of the amino terminus of CCR5 facilitates HIV-1 entry. Cell 96 667 676

19. NatsukaS

GerstenKM

ZenitaK

KannagiR

LoweJB

1994 Molecular cloning of a cDNA encoding a novel human leukocyte α-1,3-fucosyltransferase capable of synthesizing the sialyl Lewis x determinant. J Biol Chem 269 16789 16794

20. SasakiK

KurataK

FunayamaK

NagataM

WatanabeE

1994 Expression cloning of a novel α1,3-fucosyltransferase that is involved in biosynthesis of the sialyl Lewis x carbohydrate determinants in leukocytes. J Biol Chem 269 14730 14737

21. YangB

ChuangH

YangKD

2009 Sialylated glycans as receptor and inhibitor of enterovirus 71 infection to DLD-1 intestinal cells. Virol J 6 141

22. BernimoulinMP

ZengXL

AbbalC

GiraudS

MartinezM

2003 Molecular basis of leukocyte rolling on PSGL-1. Predominant role of core-2 O-glycans and of tyrosine sulfate residue 51. J Biol Chem 278 37 47

23. LeppänenA

WhiteSP

HelinJ

McEverRP

CummingsRD

2000 Binding of glycosulfopeptides to P-selectin requires stereospecific contributions of individual tyrosine sulfate and sugar residues. J Biol Chem 275 39569 39578

24. PatelKP

BergelsonJM

2009 Receptors identified for hand, foot and mouth virus. Nat Med 15 728 729

25. LinYW

WangSW

TungYY

ChenSH

2009 Enterovirus 71 infection of human dendritic cells. Exp Biol Med (Maywood) 234 1166 1173

26. BorgesE

TietzW

SteegmaierM

MollT

HallmannR

1997 P-selectin glycoprotein ligand-1 (PSGL-1) on T helper 1 but not on T helper 2 cells binds to P-selectin and supports migration into inflamed skin. J Exp Med 185 573 578

27. HirataT

Merrill-SkoloffG

AabM

YangJ

FurieBC

2000 P-selectin glycoprotein ligand 1 (PSGL-1) is a physiological ligand for E-selectin in mediating T helper 1 lymphocyte migration. J Exp Med 192 1669 1675

28. OppermannM

2004 Chemokine receptor CCR5: insights into structure, function, and regulation. Cell Signal 16 1201 1210

29. ModlinJF

2007 Enterovirus déjà vu. N Engl J Med 356 1204 1205

30. NagataN

ShimizuH

AmiY

TanoY

HarashimaA

2002 Pyramidal and extrapyramidal involvement in experimental infection of cynomolgus monkeys with enterovirus 71. J Med Virol 67 207 216

31. KehoeJW

VelappanN

WalboltM

RasmussenJ

KingD

2006 Using phage display to select antibodies recognizing post-translational modifications independently of sequence context. Mol Cell Proteomics 5 2350 2363

32. IzumiyaY

LinSF

EllisonT

ChenLY

IzumiyaC

2003 Kaposi's sarcoma-associated herpesvirus K-bZIP is a coregulator of K-Rta: physical association and promoter-dependent transcriptional repression. J Virol 77 1441 1451

33. ShimizuH

UtamaA

YoshiiK

YoshidaH

YoneyamaT

1999 Enterovirus 71 from fatal and nonfatal cases of hand, foot and mouth disease epidemics in Malaysia, Japan and Taiwan in 1997–1998. Jpn J Infect Dis 52 12 15

34. ShimizuH

UtamaA

OnnimalaN

LiC

Li-BiZ

2004 Molecular epidemiology of enterovirus 71 infection in the Western Pacific Region. Pediatr Int 46 231 235

35. MizutaK

AbikoC

MurataT

MatsuzakiY

ItagakiT

2005 Frequent importation of enterovirus 71 from surrounding countries into the local community of Yamagata, Japan, between 1998 and 2003. J Clin Microbiol 43 6171 6175

36. TagayaI

TachibanaK

1975 Epidemic of hand, foot and mouth disease in Japan, 1972–1973: difference in epidemiologic and virologic features from the previous one. Jpn J Med Sci Biol 28 231 234

37. HerreroLJ

LeeCSM

HurrelbrinkRJ

ChuaBH

ChuaKB

2003 Molecular epidemiology of enterovirus 71 in peninsular Malaysia, 1997–2000. Arch Virol 148 1369 1385

Štítky
Hygiena a epidemiológia Infekčné lekárstvo Laboratórium

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