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 LaboratóriumČlánok vyšiel v časopise
PLOS Pathogens
2010 Číslo 1
- Očkování proti virové hemoragické horečce Ebola experimentální vakcínou rVSVDG-ZEBOV-GP
- Parazitičtí červi v terapii Crohnovy choroby a dalších zánětlivých autoimunitních onemocnění
- Koronavirus hýbe světem: Víte jak se chránit a jak postupovat v případě podezření?
Najčítanejšie v tomto čísle
- Panton-Valentine Leukocidin Is a Very Potent Cytotoxic Factor for Human Neutrophils
- CD8+ T Cell Control of HIV—A Known Unknown
- Polyoma Virus-Induced Osteosarcomas in Inbred Strains of Mice: Host Determinants of Metastasis
- The Deadly Chytrid Fungus: A Story of an Emerging Pathogen