Polyomavirus capsid protein (VP1)

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Polyomaviruses are a group of small, non-enveloped DNA viruses that can infect birds, rodents, and primates. Members of the group include simian virus 40 (SV40) and murine polyomavirus (mPyV) as well as a number of human polyomaviruses such as the BK and JC viruses (BKV and JCV, respectively). Recently, a new human polyomavirus was found to be linked to Merkel cell carcinoma, an aggressive type of skin cancer[1]. All polyomavirus capsids are constructed from 360 copies of the major coat protein, VP1, arranged in pentamers on a T=7 icosahedral lattice[2]. The cell-surface receptors for SV40, mPyV, BKV, JCV, and possibly other polyomaviruses are gangliosides, which are complex, sialic acid-containing sphingolipids that reside primarily in lipid rafts. SV40 uses the ganglioside GM1, BKV binds GD1b and GT1b, and mPyV attaches to GD1a and GT1b[3][4]. Crystal structures are available for complete mPyV particles and for mPyV VP1 pentamers in complex with ganglioside receptor fragments[5][6] as well as for the SV40 VP1 pentamer in complex with GM1 [7]. The glycan-binding properties of the human polyomaviruses are currently being investigated.

The available structures show that VP1 forms a scaffold that can modulate the specificity of interaction through small changes in surface loops. We plan to generate a set of perhaps five different structures that highlight conserved as well as non-conserved interactions with different gangliosides, thereby providing a platform for understanding and altering receptor-binding properties. This work is important, as there are few known examples of viral proteins from non-enveloped viruses with a common fold for which subtle modulations of surface properties result in altered glycan-binding specificities.


CFG Participating Investigators contributing to the understanding of this paradigm

CFG Participating Investigators (PIs) contributing to the understanding of VP1 include: Niklas Arnberg, Ten Feizi, Thilo Stehle

Progress toward understanding this GBP paradigm

Carbohydrate ligands

The polyomaviruses use a range of glycans for attachment and cell entry, depending on the virus type. For the simian virus SV40 and murine polyomavirus, the receptors have been identified as gangliosides GM1 and GT1b/GD1a[3], respectively. The human BK polyomavirus binds to sialylated glycans that include gangliosides GD1b and GT1b [4][8]. The human JC polyomavirus uses sialylated glycans[9][10][11]as well as the serotonin receptor 5HT2a</sb>R[12]as attachment receptors. The receptors for other polyomaviruses, such as the recently identified Merkel Cell Polyomavirus[1], have not been characterized, but at least some of these are likely to also use glycans for cell attachment. Participating investigators (PIs) of the CFG have made major contributions to our understanding of the structural and functional basis of attachment of polyomaviruses to their receptors[3][6][13][7][14]

Cellular expression of GBP and ligands

Depending on virus type.
JC Polyomavirus: persists in the kidney [15]. In immunocompromised individuals, the virus infects glial cells, including astrocytes and the myelin-producing oligodendrocytes, resulting in the fatal disease PML (Progressive Multifocal Leukoecenlopathy) [16][17][18].
BK Polyomavirus: Infects genitourinary tract [19][20][21], causes PVN (Polyomavirus-Associated Nephropathy).

Biosynthesis of ligands

Gangliosides, sialylated oligosaccharides are synthesized by the host


A selection of gangliosides is shown below. GM1, GD1a, GD1b and GT1b are used by several polyomaviruses as receptors.

Biological roles of GBP-ligand interaction

Cell attachment, required for entry and infectivity, determinant of tropism[3] [8][4]. Recent data show that the structure of ganglioside GM1 determines SV40-induced membrane invagination and infection[22]. Subsequent entry processes depend for many polyomaviruses on proteins in the endoplasmic reticulum[23].

CFG resources used in investigations

The best examples of CFG contributions to this paradigm are described below, with links to specific data sets. For a complete list of CFG data and resources relating to this paradigm, see the CFG database search results for "polyoma".

Glycan profiling


Glycogene microarray


Knockout mouse lines


Glycan array

The CFG glycan array was used to determine the ligand specificity for SV40. This information was then used to crystallize SV40 VP1 in complex with the oligosaccharide portion of the GM1 gangloside. To see all glycan array results for VP1, click here.

Related GBPs

Functionally (but not structurally) related are the pentameric B proteins of the AB5-type toxins, such as Subtilase cytotoxin (SubAB). These also interact with gangliosides.


  1. 1.0 1.1 Feng H, Shuda M, Chang Y, Moore PS: Clonal integration of a polyomavirus in human Merkel cell carcinoma. Science 2008, 319:1096-1100.
  2. Liddington RC, Yan Y, Moulai J, Sahli R, Benjamin TL, Harrison SC: Structure of simian virus 40 at 3.8-A resolution. Nature 1991, 354:278-284.
  3. 3.0 3.1 3.2 3.3 Tsai B, Gilbert JM, Stehle T, Lencer W, Benjamin TL, Rapoport TA: Gangliosides are receptors for murine polyoma virus and SV40. Embo J 2003, 22:4346-4355.
  4. 4.0 4.1 4.2 Low JA, Magnuson B, Tsai B, Imperiale MJ: Identification of gangliosides GD1b and GT1b as receptors for BK virus. J Virol 2006, 80:1361-1366.
  5. Stehle T, Yan Y, Benjamin TL, Harrison SC: Structure of murine polyomavirus complexed with an oligosaccharide receptor fragment. Nature 1994, 369:160-163.
  6. 6.0 6.1 Stehle T, Harrison SC: High-resolution structure of a polyomavirus VP1-oligosaccharide complex: implications for assembly and receptor binding. The EMBO Journal 1997, 16:5139-5148.
  7. 7.0 7.1 Neu U, Woellner K, Gauglitz G, Stehle T: Structural basis of GM1 ganglioside recognition by simian virus 40. Proc Natl Acad Sci U S A 2008, 105:5219-5224.
  8. 8.0 8.1 Dugan AS, Eash S, Atwood WJ (2005) An N-linked glycoprotein with alpha(2,3)-linked sialic acid is a receptor for BK virus. J Virol 79: 14442-14445.
  9. Dugan AS, Gasparovic ML, Atwood WJ (2008) Direct correlation between sialic acid binding and infection of cells by two human polyomaviruses (JC virus and BK virus). J Virol 82: 2560-2564.
  10. Komagome R, Sawa H, Suzuki T, Suzuki Y, Tanaka S, et al. (2002) Oligosaccharides as receptors for JC virus. J Virol 76: 12992-13000.
  11. Liu CK, Wei G, Atwood WJ (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.
  12. Elphick GF, Querbes W, Jordan JA, Gee GV, Eash S, et al. (2004) The human polyomavirus, JCV, uses serotonin receptors to infect cells. Science 306: 1380-1383.
  13. Stehle T, Harrison SC (1996) Crystal structures of murine polyomavirus in complex with straight-chain and branched-chain sialyloligosaccharide receptor fragments. Structure, Folding and Design 4: 183-194.
  14. Neu U, Stehle T, Atwood WJ (2009) The Polyomaviridae: Contributions of virus structure to our understanding of virus receptors and infectious entry. Virology 384: 389-399.
  15. Dorries K (1998) Molecular biology and pathogenesis of human polyomavirus infections. Dev Biol Stand 94: 71-79.
  16. Silverman L, Rubinstein LJ (1965) Electron microscopic observations on a case of progressive multifocal leukoencephalopathy. Acta Neuropathol 5: 215-224.
  17. Seth P, Diaz F, Major EO (2003) Advances in the biology of JC virus and induction of progressive multifocal leukoencephalopathy. J Neurovirol 9: 236-246.
  18. Khalili K, White MK (2006) Human demyelinating disease and the polyomavirus JCV. Mult Scler 12: 133-142.
  19. Hirsch HH, Steiger J (2003) Polyomavirus BK. Lancet Infect Dis 3: 611-623.
  20. Shinohara T, Matsuda M, Cheng SH, Marshall J, Fujita M, et al. (1993) BK virus infection of the human urinary tract. J Med Virol 41: 301-305.
  21. Nickeleit V, Hirsch HH, Binet IF, Gudat F, Prince O, et al. (1999) Polyomavirus infection of renal allograft recipients: from latent infection to manifest disease. J Am Soc Nephrol 10: 1080-1089.
  22. Ewers H, Romer W, Smith AE, Bacia K, Dmitrieff S, et al. (2010) GM1 structure determines SV40-induced membrane invagination and infection. Nat Cell Biol 12: 11-18; sup pp 11-12.
  23. Schelhaas M, Malmstrom J, Pelkmans L, Haugstetter J, Ellgaard L, et al. (2007) Simian Virus 40 depends on ER protein folding and quality control factors for entry into host cells. Cell 131: 516-529.


The CFG is grateful to the following PIs for their contributions to this wiki page: Mavis McKenna, Thilo Stehle

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