Glycosaminoglycans and Sialylated Glycans Sequentially Facilitate Merkel Cell Polyomavirus Infectious Entry
Merkel cell polyomavirus (MCV or MCPyV) appears to be a causal factor in the development of Merkel cell carcinoma, a rare but highly lethal form of skin cancer. Although recent reports indicate that MCV virions are commonly shed from apparently healthy human skin, the precise cellular tropism of the virus in healthy subjects remains unclear. To begin to explore this question, we set out to identify the cellular receptors or co-receptors required for the infectious entry of MCV. Although several previously studied polyomavirus species have been shown to bind to cell surface sialic acid residues associated with glycolipids or glycoproteins, we found that sialylated glycans are not required for initial attachment of MCV virions to cultured human cell lines. Instead, glycosaminoglycans (GAGs), such as heparan sulfate (HS) and chondroitin sulfate (CS), serve as initial attachment receptors during the MCV infectious entry process. Using cell lines deficient in GAG biosynthesis, we found that N-sulfated and/or 6-O-sulfated forms of HS mediate infectious entry of MCV reporter vectors, while CS appears to be dispensable. Intriguingly, although cell lines deficient in sialylated glycans readily bind MCV capsids, the cells are highly resistant to MCV reporter vector-mediated gene transduction. This suggests that sialylated glycans play a post-attachment role in the infectious entry process. Results observed using MCV reporter vectors were confirmed using a novel system for infectious propagation of native MCV virions. Taken together, the findings suggest a model in which MCV infectious entry occurs via initial cell binding mediated primarily by HS, followed by secondary interactions with a sialylated entry co-factor. The study should facilitate the development of inhibitors of MCV infection and help shed light on the infectious entry pathways and cellular tropism of the virus.
Vyšlo v časopise:
Glycosaminoglycans and Sialylated Glycans Sequentially Facilitate Merkel Cell Polyomavirus Infectious Entry. PLoS Pathog 7(7): e32767. doi:10.1371/journal.ppat.1002161
Kategorie:
Research Article
prolekare.web.journal.doi_sk:
https://doi.org/10.1371/journal.ppat.1002161
Souhrn
Merkel cell polyomavirus (MCV or MCPyV) appears to be a causal factor in the development of Merkel cell carcinoma, a rare but highly lethal form of skin cancer. Although recent reports indicate that MCV virions are commonly shed from apparently healthy human skin, the precise cellular tropism of the virus in healthy subjects remains unclear. To begin to explore this question, we set out to identify the cellular receptors or co-receptors required for the infectious entry of MCV. Although several previously studied polyomavirus species have been shown to bind to cell surface sialic acid residues associated with glycolipids or glycoproteins, we found that sialylated glycans are not required for initial attachment of MCV virions to cultured human cell lines. Instead, glycosaminoglycans (GAGs), such as heparan sulfate (HS) and chondroitin sulfate (CS), serve as initial attachment receptors during the MCV infectious entry process. Using cell lines deficient in GAG biosynthesis, we found that N-sulfated and/or 6-O-sulfated forms of HS mediate infectious entry of MCV reporter vectors, while CS appears to be dispensable. Intriguingly, although cell lines deficient in sialylated glycans readily bind MCV capsids, the cells are highly resistant to MCV reporter vector-mediated gene transduction. This suggests that sialylated glycans play a post-attachment role in the infectious entry process. Results observed using MCV reporter vectors were confirmed using a novel system for infectious propagation of native MCV virions. Taken together, the findings suggest a model in which MCV infectious entry occurs via initial cell binding mediated primarily by HS, followed by secondary interactions with a sialylated entry co-factor. The study should facilitate the development of inhibitors of MCV infection and help shed light on the infectious entry pathways and cellular tropism of the virus.
Zdroje
1. BauerPHCuiCLiuWRStehleTHarrisonSC 1999 Discrimination between sialic acid-containing receptors and pseudoreceptors regulates polyomavirus spread in the mouse. J Virol 73 5826 5832
2. SappMDayPM 2009 Structure, attachment and entry of polyoma- and papillomaviruses. Virology 384 400 409
3. NeuUMaginnisMSPalmaASStrohLJNelsonCD 2010 Structure-function analysis of the human JC polyomavirus establishes the LSTc pentasaccharide as a functional receptor motif. Cell Host Microbe 8 309 319
4. ChenBJAtwoodWJ 2002 Construction of a novel JCV/SV40 hybrid virus (JCSV) reveals a role for the JCV capsid in viral tropism. Virology 300 282 290
5. NakanishiAChapellierBMaekawaNHiramotoMKugeT 2008 SV40 vectors carrying minimal sequence of viral origin with exchangeable capsids. Virology 379 110 117
6. SchmidtMChioriniJA 2006 Gangliosides are essential for bovine adeno-associated virus entry. J Virol 80 5516 5522
7. KaludovNBrownKEWaltersRWZabnerJChioriniJA 2001 Adeno-associated virus serotype 4 (AAV4) and AAV5 both require sialic acid binding for hemagglutination and efficient transduction but differ in sialic acid linkage specificity. J Virol 75 6884 6893
8. SummerfordCSamulskiRJ 1998 Membrane-associated heparan sulfate proteoglycan is a receptor for adeno-associated virus type 2 virions. J Virol 72 1438 1445
9. HarbisonCEChioriniJAParrishCR 2008 The parvovirus capsid odyssey: from the cell surface to the nucleus. Trends Microbiol 16 208 214
10. WakabayashiHNatsukaSMegaTOtsukiNIsajiM 1999 Novel proteoglycan linkage tetrasaccharides of human urinary soluble thrombomodulin, SO4-3GlcAbeta1-3Galbeta1-3(+/−Siaalpha2-6)Galbeta1-4Xyl. J Biol Chem 274 5436 5442
11. EskoJDKimataKLindahlU 2009 Proteoglycans and Sulfated Glycosaminoglycans. VarkiACREskoJDFreezeHHStanleyPBertozziCRHartGWEtzlerME Essentials of Glycobiology. second ed Cold Spring Harbor Cold Spring Harbor Laboratory Press 229 248
12. WuZAsokanAGriegerJCGovindasamyLAgbandje-McKennaM 2006 Single amino acid changes can influence titer, heparin binding, and tissue tropism in different adeno-associated virus serotypes. J Virol 80 11393 11397
13. WuZMillerEAgbandje-McKennaMSamulskiRJ 2006 Alpha2,3 and alpha2,6 N-linked sialic acids facilitate efficient binding and transduction by adeno-associated virus types 1 and 6. J Virol 80 9093 9103
14. GaynorAMNissenMDWhileyDMMackayIMLambertSB 2007 Identification of a novel polyomavirus from patients with acute respiratory tract infections. PLoS Pathog 3 e64
15. AllanderTAndreassonKGuptaSBjerknerABogdanovicG 2007 Identification of a third human polyomavirus. J Virol 81 4130 4136
16. FengHShudaMChangYMoorePS 2008 Clonal integration of a polyomavirus in human Merkel cell carcinoma. Science 319 1096 1100
17. SchowalterRMPastranaDVPumphreyKAMoyerALBuckCB 2010 Merkel cell polyomavirus and two previously unknown polyomaviruses are chronically shed from human skin. Cell Host Microbe 7 509 515
18. van der MeijdenEJanssensRWLauberCBouwes BavinckJNGorbalenyaAE 2010 Discovery of a new human polyomavirus associated with trichodysplasia spinulosa in an immunocompromized patient. PLoS Pathog 6 e1001024
19. ScudaNHofmannJCalvignac-SpencerSRuprechtKLimanP 2011 A novel human polyomavirus closely related to the african green monkey-derived lymphotropic polyomavirus. J Virol 85 4586 4590
20. HoubenRSchramaDBeckerJC 2009 Molecular pathogenesis of Merkel cell carcinoma. Exp Dermatol 18 193 198
21. WielandUMauchCKreuterAKriegTPfisterH 2009 Merkel cell polyomavirus DNA in persons without merkel cell carcinoma. Emerg Infect Dis 15 1496 1498
22. LoyoMGuerrero-PrestonRBraitMHoqueMChuangA 2009 Quantitative detection of merkel cell virus in human tissues and possible mode of transmission. Int J Cancer 126 2991 2996
23. EricksonKDGarceaRLTsaiB 2009 Ganglioside GT1b is a putative host cell receptor for the Merkel cell polyomavirus. J Virol 83 10275 10279
24. LowJAMagnusonBTsaiBImperialeMJ 2006 Identification of gangliosides GD1b and GT1b as receptors for BK virus. J Virol 80 1361 1366
25. PastranaDVTolstovYLBeckerJCMoorePSChangY 2009 Quantitation of human seroresponsiveness to Merkel cell polyomavirus. PLoS Pathog 5 e1000578
26. TolstovYLPastranaDVFengHBeckerJCJenkinsFJ 2009 Human Merkel cell polyomavirus infection II. MCV is a common human infection that can be detected by conformational capsid epitope immunoassays. Int J Cancer 125 1250 1256
27. FavreMBreitburdFCroissantOOrthG 1974 Hemagglutinating activity of bovine papilloma virus. Virology 60 572 578
28. SinibaldiLVitiDGoldoniPCavalloGCaroniC 1987 Inhibition of BK virus haemagglutination by gangliosides. J Gen Virol 68 Pt 3 879 883
29. NakanishiAItohNLiPPHandaHLiddingtonRC 2007 Minor capsid proteins of simian virus 40 are dispensable for nucleocapsid assembly and cell entry but are required for nuclear entry of the viral genome. J Virol 81 3778 3785
30. BuckCBPastranaDVLowyDRSchillerJT 2004 Efficient intracellular assembly of papillomaviral vectors. J Virol 78 751 757
31. UchidaYTsukadaYSugimoriT 1979 Enzymatic properties of neuraminidases from Arthrobacter ureafaciens. J Biochem 86 1573 1585
32. Miller-PodrazaHBradleyRMFishmanPH 1982 Biosynthesis and localization of gangliosides in cultured cells. Biochemistry 21 3260 3265
33. EckhardtMGotzaBGerardy-SchahnR 1998 Mutants of the CMP-sialic acid transporter causing the Lec2 phenotype. J Biol Chem 273 20189 20195
34. Rosales FritzVMDaniottiJLMaccioniHJ 1997 Chinese hamster ovary cells lacking GM1 and GD1a synthesize gangliosides upon transfection with human GM2 synthase. Biochim Biophys Acta 1354 153 158
35. YoungWWJrLutzMSMillsSELechler-OsbornS 1990 Use of brefeldin A to define sites of glycosphingolipid synthesis: GA2/GM2/GD2 synthase is trans to the brefeldin A block. Proc Natl Acad Sci U S A 87 6838 6842
36. BuckCBThompsonCDRobertsJNMullerMLowyDR 2006 Carrageenan is a potent inhibitor of papillomavirus infection. PLoS Pathog 2 e69
37. GiroglouTFlorinLSchaferFStreeckRESappM 2001 Human papillomavirus infection requires cell surface heparan sulfate. J Virol 75 1565 1570
38. ShawGMorseSAraratMGrahamFL 2002 Preferential transformation of human neuronal cells by human adenoviruses and the origin of HEK 293 cells. FASEB J 16 869 871
39. JohnsonKMKinesRCRobertsJNLowyDRSchillerJT 2009 Role of heparan sulfate in attachment to and infection of the murine female genital tract by human papillomavirus. J Virol 83 2067 2074
40. SafaiyanFKolsetSOPrydzKGottfridssonELindahlU 1999 Selective effects of sodium chlorate treatment on the sulfation of heparan sulfate. J Biol Chem 274 36267 36273
41. EskoJBertozziCR 2009 Chemical Tools for Inhibiting Glycosylation. VarkiACREskoJDFreezeHHStanleyPBertozziCRHartGWEtzlerME Essentials of Glycobiology. second ed Cold Spring Harbor Cold Spring Harbor Laboratory Press 705 718
42. BameKJEskoJD 1989 Undersulfated heparan sulfate in a Chinese hamster ovary cell mutant defective in heparan sulfate N-sulfotransferase. J Biol Chem 264 8059 8065
43. EskoJDStewartTETaylorWH 1985 Animal cell mutants defective in glycosaminoglycan biosynthesis. Proc Natl Acad Sci U S A 82 3197 3201
44. LidholtKWeinkeJLKiserCSLugemwaFNBameKJ 1992 A single mutation affects both N-acetylglucosaminyltransferase and glucuronosyltransferase activities in a Chinese hamster ovary cell mutant defective in heparan sulfate biosynthesis. Proc Natl Acad Sci U S A 89 2267 2271
45. BaiXEskoJD 1996 An animal cell mutant defective in heparan sulfate hexuronic acid 2-O-sulfation. J Biol Chem 271 17711 17717
46. LindahlULiJP 2009 Interactions between heparan sulfate and proteins-design and functional implications. Int Rev Cell Mol Biol 276 105 159
47. SelinkaHCGiroglouTNowakTChristensenNDSappM 2003 Further evidence that papillomavirus capsids exist in two distinct conformations. J Virol 77 12961 12967
48. PiepkornMHovinghPLinkerA 1988 Evidence for independent metabolism and cell surface localization of cell surface localization of cellular proteoglycans and glycosaminoglycan free chains. J Cell Physiol 135 189 199
49. Vander KooiCWJusinoMAPermanBNeauDBBellamyHD 2007 Structural basis for ligand and heparin binding to neuropilin B domains. Proc Natl Acad Sci U S A 104 6152 6157
50. KrillekeDDeErkenezASchubertWGiriIRobinsonGS 2007 Molecular mapping and functional characterization of the VEGF164 heparin-binding domain. J Biol Chem 282 28045 28056
51. MurakamiPMcCamanMT 1999 Quantitation of adenovirus DNA and virus particles with the PicoGreen fluorescent Dye. Anal Biochem 274 283 288
52. DoorbarJ 2005 The papillomavirus life cycle. J Clin Virol 32 Suppl 1 S7 15
53. PastranaDVPumphreyKACuburuNSchowalterRMBuckCB 2010 Characterization of monoclonal antibodies specific for the Merkel cell polyomavirus capsid. Virology 405 20 25
54. ElphickGFQuerbesWJordanJAGeeGVEashS 2004 The human polyomavirus, JCV, uses serotonin receptors to infect cells. Science 306 1380 1383
55. LiuCKWeiGAtwoodWJ 1998 Infection of glial cells by the human polyomavirus JC is mediated by an N-linked glycoprotein containing terminal alpha(2–6)-linked sialic acids. J Virol 72 4643 4649
56. TsaiBGilbertJMStehleTLencerWBenjaminTL 2003 Gangliosides are receptors for murine polyoma virus and SV40. EMBO J 22 4346 4355
57. HaunGKepplerOTBockCTHerrmannMZentgrafH 1993 The cell surface receptor is a major determinant restricting the host range of the B-lymphotropic papovavirus. J Virol 67 7482 7492
58. DowdKAPiersonTC 2011 Antibody-mediated neutralization of flaviviruses: a reductionist view. Virology 411 306 315
59. LambertSBouttierMVassyRSeigneuretMPetrow-SadowskiC 2009 HTLV-1 uses HSPG and neuropilin-1 for entry by molecular mimicry of VEGF165. Blood 113 5176 5185
60. SchillerJTDayPMKinesRC 2010 Current understanding of the mechanism of HPV infection. Gynecol Oncol 118 S12 17
61. zur HausenH 2009 Papillomaviruses in the causation of human cancers - a brief historical account. Virology 384 260 265
62. ShudaMAroraRKwunHJFengHSaridR 2009 Human Merkel cell polyomavirus infection I. MCV T antigen expression in Merkel cell carcinoma, lymphoid tissues and lymphoid tumors. Int J Cancer 125 1243 1249
63. BuckCBThompsonCD 2007 Production of papillomavirus-based gene transfer vectors. Curr Protoc Cell Biol Chapter 26 Unit 26.21
64. ZhongSRandhawaPSIkegayaHChenQZhengHY 2009 Distribution patterns of BK polyomavirus (BKV) subtypes and subgroups in American, European and Asian populations suggest co-migration of BKV and the human race. J Gen Virol 90 144 152
65. BuckCBThompsonCDPangYYLowyDRSchillerJT 2005 Maturation of papillomavirus capsids. J Virol 79 2839 2846
66. HamiltonRSGravellMMajorEO 2000 Comparison of antibody titers determined by hemagglutination inhibition and enzyme immunoassay for JC virus and BK virus. J Clin Microbiol 38 105 109
67. AradU 1998 Modified Hirt procedure for rapid purification of extrachromosomal DNA from mammalian cells. Biotechniques 24 760 762
Štítky
Hygiena a epidemiológia Infekčné lekárstvo LaboratóriumČlánok vyšiel v časopise
PLOS Pathogens
2011 Číslo 7
- 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
- Requires Glycerol for Maximum Fitness During The Tick Phase of the Enzootic Cycle
- Comparative Genomics Yields Insights into Niche Adaptation of Plant Vascular Wilt Pathogens
- The Role of IL-15 Deficiency in the Pathogenesis of Virus-Induced Asthma Exacerbations
- “Persisters”: Survival at the Cellular Level