#PAGE_PARAMS# #ADS_HEAD_SCRIPTS# #MICRODATA#

The M/GP Glycoprotein Complex of Porcine Reproductive and Respiratory Syndrome Virus Binds the Sialoadhesin Receptor in a Sialic Acid-Dependent Manner


The porcine reproductive and respiratory syndrome virus (PRRSV) is a major threat to swine health worldwide and is considered the most significant viral disease in the swine industry today. In past years, studies on the entry of the virus into its host cell have led to the identification of a number of essential virus receptors and entry mediators. However, viral counterparts for these molecules have remained elusive and this has made rational development of new generation vaccines impossible. The main objective of this study was to identify the viral counterparts for sialoadhesin, a crucial PRRSV receptor on macrophages. For this purpose, a soluble form of sialoadhesin was constructed and validated. The soluble sialoadhesin could bind PRRSV in a sialic acid-dependent manner and could neutralize PRRSV infection of macrophages, thereby confirming the role of sialoadhesin as an essential PRRSV receptor on macrophages. Although sialic acids are present on the GP3, GP4 and GP5 envelope glycoproteins, only the M/GP5 glycoprotein complex of PRRSV was identified as a ligand for sialoadhesin. The interaction was found to be dependent on the sialic acid binding capacity of sialoadhesin and on the presence of sialic acids on GP5. These findings not only contribute to a better understanding of PRRSV biology, but the knowledge and tools generated in this study also hold the key to the development of a new generation of PRRSV vaccines.


Vyšlo v časopise: The M/GP Glycoprotein Complex of Porcine Reproductive and Respiratory Syndrome Virus Binds the Sialoadhesin Receptor in a Sialic Acid-Dependent Manner. PLoS Pathog 6(1): e32767. doi:10.1371/journal.ppat.1000730
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1000730

Souhrn

The porcine reproductive and respiratory syndrome virus (PRRSV) is a major threat to swine health worldwide and is considered the most significant viral disease in the swine industry today. In past years, studies on the entry of the virus into its host cell have led to the identification of a number of essential virus receptors and entry mediators. However, viral counterparts for these molecules have remained elusive and this has made rational development of new generation vaccines impossible. The main objective of this study was to identify the viral counterparts for sialoadhesin, a crucial PRRSV receptor on macrophages. For this purpose, a soluble form of sialoadhesin was constructed and validated. The soluble sialoadhesin could bind PRRSV in a sialic acid-dependent manner and could neutralize PRRSV infection of macrophages, thereby confirming the role of sialoadhesin as an essential PRRSV receptor on macrophages. Although sialic acids are present on the GP3, GP4 and GP5 envelope glycoproteins, only the M/GP5 glycoprotein complex of PRRSV was identified as a ligand for sialoadhesin. The interaction was found to be dependent on the sialic acid binding capacity of sialoadhesin and on the presence of sialic acids on GP5. These findings not only contribute to a better understanding of PRRSV biology, but the knowledge and tools generated in this study also hold the key to the development of a new generation of PRRSV vaccines.


Zdroje

1. CollinsJE

BenfieldDA

ChristiansonWT

HarrisL

HenningsJC

1992 Isolation of swine infertility and respiratory syndrome virus (isolate ATCC VR-2332) in North America and experimental reproduction of the disease in gnotobiotic pigs. J Vet Diagn Invest 4 117 126

2. WensvoortG

TerpstraC

PolJM

ter LaakEA

BloemraadM

1991 Mystery swine disease in The Netherlands: the isolation of Lelystad virus. Vet Q 13 121 130

3. CavanaghD

1997 Nidovirales: a new order comprising Coronaviridae and Arteriviridae. Arch Virol 142 629 633

4. NeumannEJ

KliebensteinJB

JohnsonCD

MabryJW

BushEJ

2005 Assessment of the economic impact of porcine reproductive and respiratory syndrome on swine production in the United States. J Am Vet Med Assoc 227 385 392

5. LiY

WangX

BoK

WangX

TangB

2007 Emergence of a highly pathogenic porcine reproductive and respiratory syndrome virus in the Mid-Eastern region of China. Vet J 174 577 584

6. TianK

YuX

ZhaoT

FengY

CaoZ

2007 Emergence of fatal PRRSV variants: unparalleled outbreaks of atypical PRRS in China and molecular dissection of the unique hallmark. PLoS ONE 2 e526 doi:10.1371/journal.pone.0000526

7. ZhouYJ

HaoXF

TianZJ

TongGZ

YooD

2008 Highly virulent porcine reproductive and respiratory syndrome virus emerged in China. Transbound Emerg Dis 55 152 164

8. BotnerA

StrandbygaardB

SorensenKJ

HaveP

MadsenKG

1997 Appearance of acute PRRS-like symptoms in sow herds after vaccination with a modified live PRRS vaccine. Vet Rec 141 497 499

9. NielsenHS

OleksiewiczMB

ForsbergR

StadejekT

BotnerA

2001 Reversion of a live porcine reproductive and respiratory syndrome virus vaccine investigated by parallel mutations. J Gen Virol 82 1263 1272

10. ScorttiM

PrietoC

Martinez-LoboFJ

SimarroI

CastroJM

2006 Effects of two commercial European modified-live vaccines against porcine reproductive and respiratory syndrome viruses in pregnant gilts. Vet J 172 506 514

11. LabarqueG

ReethKV

NauwynckH

DrexlerC

Van GuchtS

2004 Impact of genetic diversity of European-type porcine reproductive and respiratory syndrome virus strains on vaccine efficacy. Vaccine 22 4183 4190

12. MengelingWL

LagerKM

VorwaldAC

KoehlerKJ

2003 Strain specificity of the immune response of pigs following vaccination with various strains of porcine reproductive and respiratory syndrome virus. Vet Microbiol 93 13 24

13. NilubolD

PlattKB

HalburPG

TorremorellM

HarrisDL

2004 The effect of a killed porcine reproductive and respiratory syndrome virus (PRRSV) vaccine treatment on virus shedding in previously PRRSV infected pigs. Vet Microbiol 102 11 18

14. ScorttiM

PrietoC

AlvarezE

SimarroI

CastroJM

2007 Failure of an inactivated vaccine against porcine reproductive and respiratory syndrome to protect gilts against a heterologous challenge with PRRSV. Vet Rec 161 809 813

15. ZuckermannFA

GarciaEA

LuqueID

Christopher-HenningsJ

DosterA

2007 Assessment of the efficacy of commercial porcine reproductive and respiratory syndrome virus (PRRSV) vaccines based on measurement of serologic response, frequency of gamma-IFN-producing cells and virological parameters of protection upon challenge. Vet Microbiol 123 69 85

16. BenfieldDA

NelsonE

CollinsJE

HarrisL

GoyalSM

1992 Characterization of swine infertility and respiratory syndrome (SIRS) virus (isolate ATCC VR-2332). J Vet Diagn Invest 4 127 133

17. DeaS

SawyerN

AlainR

AthanassiousR

1995 Ultrastructural characteristics and morphogenesis of porcine reproductive and respiratory syndrome virus propagated in the highly permissive MARC-145 cell clone. Adv Exp Med Biol 380 95 98

18. MardassiH

AthanassiousR

MounirS

DeaS

1994 Porcine reproductive and respiratory syndrome virus: morphological, biochemical and serological characteristics of Quebec isolates associated with acute and chronic outbreaks of porcine reproductive and respiratory syndrome. Can J Vet Res 58 55 64

19. MeulenbergJJ

HulstMM

de MeijerEJ

MoonenPL

den BestenA

1993 Lelystad virus, the causative agent of porcine epidemic abortion and respiratory syndrome (PEARS), is related to LDV and EAV. Virology 192 62 72

20. WensvoortG

de KluyverEP

PolJM

WagenaarF

MoormannRJ

1992 Lelystad virus, the cause of porcine epidemic abortion and respiratory syndrome: a review of mystery swine disease research at Lelystad. Vet Microbiol 33 185 193

21. SnijderEJ

SpaanWJM

2007 Arteriviruses.

KnipeDM

HowleyPM

Fields Virology, Fifth Edition Philadelphia Lippincott Williams & Wilkins 1337 1355

22. de LimaM

AnsariIH

DasPB

KuBJ

Martinez-LoboFJ

2009 GP3 is a structural component of the PRRSV type II (US) virion. Virology 390 31 36

23. WissinkEH

KroeseMV

van WijkHA

RijsewijkFA

MeulenbergJJ

2005 Envelope protein requirements for the assembly of infectious virions of porcine reproductive and respiratory syndrome virus. J Virol 79 12495 12506

24. GoninP

MardassiH

GagnonCA

MassieB

DeaS

1998 A nonstructural and antigenic glycoprotein is encoded by ORF3 of the IAF-Klop strain of porcine reproductive and respiratory syndrome virus. Arch Virol 143 1927 1940

25. MardassiH

MassieB

DeaS

1996 Intracellular synthesis, processing, and transport of proteins encoded by ORFs 5 to 7 of porcine reproductive and respiratory syndrome virus. Virology 221 98 112

26. VerheijeMH

2002 Genetic engineering of the porcine reproductive and respiratory syndrome virus: exploration of avenues towards a vaccine. Dissertation, Utrecht University, The Netherlands

27. MeulenbergJJ

Petersen-den BestenA

1996 Identification and characterization of a sixth structural protein of Lelystad virus: the glycoprotein GP2 encoded by ORF2 is incorporated in virus particles. Virology 225 44 51

28. van NieuwstadtAP

MeulenbergJJ

van Essen-ZanbergenA

Petersen-den BestenA

BendeRJ

1996 Proteins encoded by open reading frames 3 and 4 of the genome of Lelystad virus (Arteriviridae) are structural proteins of the virion. J Virol 70 4767 4772

29. WuWH

FangY

FarwellR

Steffen-BienM

RowlandRR

2001 A 10-kDa structural protein of porcine reproductive and respiratory syndrome virus encoded by ORF2b. Virology 287 183 191

30. DuanX

NauwynckHJ

PensaertMB

1997 Virus quantification and identification of cellular targets in the lungs and lymphoid tissues of pigs at different time intervals after inoculation with porcine reproductive and respiratory syndrome virus (PRRSV). Vet Microbiol 56 9 19

31. TeifkeJP

DauberM

FichtnerD

LenkM

PolsterU

2001 Detection of European porcine reproductive and respiratory syndrome virus in porcine alveolar macrophages by two-colour immunofluorescence and in-situ hybridization-immunohistochemistry double labelling. J Comp Pathol 124 238 245

32. KimHS

KwangJ

YoonIJ

JooHS

FreyML

1993 Enhanced replication of porcine reproductive and respiratory syndrome (PRRS) virus in a homogeneous subpopulation of MA-104 cell line. Arch Virol 133 477 483

33. DelputtePL

CostersS

NauwynckHJ

2005 Analysis of porcine reproductive and respiratory syndrome virus attachment and internalization: distinctive roles for heparan sulphate and sialoadhesin. J Gen Virol 86 1441 1445

34. DelputtePL

VanderheijdenN

NauwynckHJ

PensaertMB

2002 Involvement of the matrix protein in attachment of porcine reproductive and respiratory syndrome virus to a heparinlike receptor on porcine alveolar macrophages. J Virol 76 4312 4320

35. VanderheijdenN

DelputteP

NauwynckH

PensaertM

2001 Effects of heparin on the entry of porcine reproductive and respiratory syndrome virus into alveolar macrophages. Adv Exp Med Biol 494 683 689

36. VanderheijdenN

DelputtePL

FavoreelHW

VandekerckhoveJ

Van DammeJ

2003 Involvement of sialoadhesin in entry of porcine reproductive and respiratory syndrome virus into porcine alveolar macrophages. J Virol 77 8207 8215

37. NauwynckHJ

DuanX

FavoreelHW

Van OostveldtP

PensaertMB

1999 Entry of porcine reproductive and respiratory syndrome virus into porcine alveolar macrophages via receptor-mediated endocytosis. J Gen Virol 80 297 305

38. DelputtePL

Van BreedamW

DelrueI

OetkeC

CrockerPR

2007 Porcine arterivirus attachment to the macrophage-specific receptor sialoadhesin is dependent on the sialic acid-binding activity of the N-terminal immunoglobulin domain of sialoadhesin. J Virol 81 9546 9550

39. DelputtePL

NauwynckHJ

2004 Porcine arterivirus infection of alveolar macrophages is mediated by sialic acid on the virus. J Virol 78 8094 8101

40. Van GorpH

Van BreedamW

DelputtePL

NauwynckHJ

2008 Sialoadhesin and CD163 join forces during entry of the porcine reproductive and respiratory syndrome virus. J Gen Virol 89 2943 2953

41. CalvertJG

SladeDE

ShieldsSL

JolieR

MannanRM

2007 CD163 expression confers susceptibility to porcine reproductive and respiratory syndrome viruses. J Virol 81 7371 7379

42. KreutzLC

AckermannMR

1996 Porcine reproductive and respiratory syndrome virus enters cells through a low pH-dependent endocytic pathway. Virus Res 42 137 147

43. MisinzoGM

DelputtePL

NauwynckHJ

2008 Involvement of proteases in porcine reproductive and respiratory syndrome virus uncoating upon internalization in primary macrophages. Vet Res 39 55

44. DuanX

NauwynckHJ

FavoreelHW

PensaertMB

1998 Identification of a putative receptor for porcine reproductive and respiratory syndrome virus on porcine alveolar macrophages. J Virol 72 4520 4523

45. CostersS

2008 Strategies exhibited by PRRSV allowing evasion of immune detection and/or clearance in the infected pig. Dissertation, Ghent University, Belgium.

46. Wieczorek-KrohmerM

WeilandF

ConzelmannK

KohlD

VisserN

1996 Porcine reproductive and respiratory syndrome virus (PRRSV): monoclonal antibodies detect common epitopes on two viral proteins of European and U.S. isolates. Vet Microbiol 51 257 266

47. NauwynckHJ

PensaertMB

1995 Effect of specific antibodies on the cell-associated spread of pseudorabies virus in monolayers of different cell types. Arch Virol 140 1137 1146

48. LefebvreDJ

CostersS

Van DoorsselaereJ

MisinzoG

DelputtePL

2008 Antigenic differences among porcine circovirus type 2 strains, as demonstrated by the use of monoclonal antibodies. J Gen Virol 89 177 187

49. HartnellA

SteelJ

TurleyH

JonesM

JacksonDG

2001 Characterization of human sialoadhesin, a sialic acid binding receptor expressed by resident and inflammatory macrophage populations. Blood 97 288 296

50. ZhangJQ

NicollG

JonesC

CrockerPR

2000 Siglec-9, a novel sialic acid binding member of the immunoglobulin superfamily expressed broadly on human blood leukocytes. J Biol Chem 275 22121 22126

51. ZhangJQ

BiedermannB

NitschkeL

CrockerPR

2004 The murine inhibitory receptor mSiglec-E is expressed broadly on cells of the innate immune system whereas mSiglec-F is restricted to eosinophils. Eur J Immunol 34 1175 1184

52. KelmS

PelzA

SchauerR

FilbinMT

TangS

1994 Sialoadhesin, myelin-associated glycoprotein and CD22 define a new family of sialic acid-dependent adhesion molecules of the immunoglobulin superfamily. Curr Biol 4 965 972

53. DuanX

NauwynckHJ

PensaertMB

1997 Effects of origin and state of differentiation and activation of monocytes/macrophages on their susceptibility to porcine reproductive and respiratory syndrome virus (PRRSV). Arch Virol 142 2483 2497

54. MurtaughMP

XiaoZ

ZuckermannF

2002 Immunological responses of swine to porcine reproductive and respiratory syndrome virus infection. Viral Immunol 15 533 547

55. DuanX

NauwynckHJ

FavoreelH

PensaertMB

1998 Porcine reproductive and respiratory syndrome virus infection of alveolar macrophages can be blocked by monoclonal antibodies against cell surface antigens. Adv Exp Med Biol 440 81 88

56. FortM

SibilaM

AllepuzA

MateuE

RoerinkF

2008 Porcine circovirus type 2 (PCV2) vaccination of conventional pigs prevents viremia against PCV2 isolates of different genotypes and geographic origins. Vaccine 26 1063 1071

57. FortM

SibilaM

Perez-MartinE

NofrariasM

MateuE

2009 One dose of a porcine circovirus 2 (PCV2) sub-unit vaccine administered to 3-week-old conventional piglets elicits cell-mediated immunity and significantly reduces PCV2 viremia in an experimental model. Vaccine 27 4031 4037

58. KixmollerM

RitzmannM

EddicksM

SaalmullerA

ElbersK

2008 Reduction of PMWS-associated clinical signs and co-infections by vaccination against PCV2. Vaccine 26 3443 3451

59. BoumaA

de SmitAJ

de KluijverEP

TerpstraC

MoormannRJ

1999 Efficacy and stability of a subunit vaccine based on glycoprotein E2 of classical swine fever virus. Vet Microbiol 66 101 114

60. DeaS

GagnonCA

MardassiH

PirzadehB

RoganD

2000 Current knowledge on the structural proteins of porcine reproductive and respiratory syndrome (PRRS) virus: comparison of the North American and European isolates. Arch Virol 145 659 688

61. MeulenbergJJ

Petersen-den BestenA

De KluyverEP

MoormannRJ

SchaaperWM

1995 Characterization of proteins encoded by ORFs 2 to 7 of Lelystad virus. Virology 206 155 163

62. WissinkEH

KroeseMV

Maneschijn-BonsingJG

MeulenbergJJ

van RijnPA

2004 Significance of the oligosaccharides of the porcine reproductive and respiratory syndrome virus glycoproteins GP2a and GP5 for infectious virus production. J Gen Virol 85 3715 3723

63. AnsariIH

KwonB

OsorioFA

PattnaikAK

2006 Influence of N-linked glycosylation of porcine reproductive and respiratory syndrome virus GP5 on virus infectivity, antigenicity, and ability to induce neutralizing antibodies. J Virol 80 3994 4004

64. PlagemannPG

RowlandRR

FaabergKS

2002 The primary neutralization epitope of porcine respiratory and reproductive syndrome virus strain VR-2332 is located in the middle of the GP5 ectodomain. Arch Virol 147 2327 2347

65. OstrowskiM

GaleotaJA

JarAM

PlattKB

OsorioFA

2002 Identification of neutralizing and nonneutralizing epitopes in the porcine reproductive and respiratory syndrome virus GP5 ectodomain. J Virol 76 4241 4250

66. PlagemannPG

2004 The primary GP5 neutralization epitope of North American isolates of porcine reproductive and respiratory syndrome virus. Vet Immunol Immunopathol 102 263 275

67. LarochelleR

D'AllaireS

MagarR

2003 Molecular epidemiology of porcine reproductive and respiratory syndrome virus (PRRSV) in Quebec. Virus Res 96 3 14

68. ChangCC

YoonKJ

ZimmermanJJ

HarmonKM

DixonPM

2002 Evolution of porcine reproductive and respiratory syndrome virus during sequential passages in pigs. J Virol 76 4750 4763

69. StadejekT

StankeviciusA

StorgaardT

OleksiewiczMB

BelakS

2002 Identification of radically different variants of porcine reproductive and respiratory syndrome virus in Eastern Europe: towards a common ancestor for European and American viruses. J Gen Virol 83 1861 1873

70. PeschS

MeyerC

OhlingerVF

2005 New insights into the genetic diversity of European porcine reproductive and respiratory syndrome virus (PRRSV). Vet Microbiol 107 31 48

71. DelputtePL

MeertsP

CostersS

NauwynckHJ

2004 Effect of virus-specific antibodies on attachment, internalization and infection of porcine reproductive and respiratory syndrome virus in primary macrophages. Vet Immunol Immunopathol 102 179 188

72. VarkiA

1997 Sialic acids as ligands in recognition phenomena. Faseb J 11 248 255

73. CrockerPR

PaulsonJC

VarkiA

2007 Siglecs and their roles in the immune system. Nat Rev Immunol 7 255 266

74. CrockerPR

RedelinghuysP

2008 Siglecs as positive and negative regulators of the immune system. Biochem Soc Trans 36 1467 1471

75. MeulenbergJJ

2000 PRRSV, the virus. Vet Res 31 11 21

Štítky
Hygiena a epidemiológia Infekčné lekárstvo Laboratórium

Článok vyšiel v časopise

PLOS Pathogens


2010 Číslo 1
Najčítanejšie tento týždeň
Najčítanejšie v tomto čísle
Kurzy

Zvýšte si kvalifikáciu online z pohodlia domova

Získaná hemofilie - Povědomí o nemoci a její diagnostika
nový kurz

Eozinofilní granulomatóza s polyangiitidou
Autori: doc. MUDr. Martina Doubková, Ph.D.

Všetky kurzy
Prihlásenie
Zabudnuté heslo

Zadajte e-mailovú adresu, s ktorou ste vytvárali účet. Budú Vám na ňu zasielané informácie k nastaveniu nového hesla.

Prihlásenie

Nemáte účet?  Registrujte sa

#ADS_BOTTOM_SCRIPTS#