Polyomavirus capsid protein (VP1) - Revision history

Kurt Drickamer: /* Glycan profiling */

2011-04-09T11:35:19Z

Glycan profiling

Kurt Drickamer: /* Knockout mouse lines */

2011-04-09T11:35:04Z

Knockout mouse lines

Kurt Drickamer: /* Glycan profiling */

2011-04-09T11:34:43Z

Glycan profiling

Kurt Drickamer: /* Biological roles of GBP-ligand interaction */

2011-04-09T11:34:23Z

Biological roles of GBP-ligand interaction

Kurt Drickamer: /* Biosynthesis of ligands */

2011-04-09T11:33:51Z

Biosynthesis of ligands

Carole Weaver: /* Glycogene microarray */

2011-03-30T23:23:38Z

Glycogene microarray

Carole Weaver at 18:23, 21 September 2010

2010-09-21T18:23:59Z

Carole Weaver: /* Carbohydrate ligands */

2010-07-02T17:37:36Z

Carbohydrate ligands

Carole Weaver: /* Structure */

2010-07-02T17:37:02Z

Structure

Carole Weaver: /* Biosynthesis of ligands */

2010-07-02T17:36:50Z

Biosynthesis of ligands

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 === Glycan profiling ===
 N/A
 <br>

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 === Knockout mouse lines ===
+None
 <br>
 === Glycan array ===

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 === Glycan profiling ===
 <br>
 === Glycogene microarray ===

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 === Biological roles of GBP-ligand interaction ===
+Cell attachment, required for entry and infectivity, determinant of tropism<ref name=" Tsai B4346 "></ref> <ref name=" Dugan AS 14442"></ref><ref name=" Low JA1361 "></ref>. Recent data show that the structure of ganglioside GM1 determines SV40-induced membrane invagination and infection<ref>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.</ref>. Subsequent entry processes depend for many polyomaviruses on proteins in the endoplasmic reticulum<ref> 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.</ref>.
 <br>
 == CFG resources used in investigations ==

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 === Biosynthesis of ligands ===
+Gangliosides, sialylated oligosaccharides, are synthesized by the host by well defined pathways ([http://www.functionalglycomics.org/glycomics/molecule/jsp/glycoEnzyme/geMolecule.jsp?slideNumber=slide9 Glucosylceramide biosynthetic pathways]).
+<br>
 === Structure ===

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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<ref name=" Feng H1096">
-Feng H, Shuda M, Chang Y, Moore PS: Clonal integration of a polyomavirus in human Merkel cell carcinoma. Science 2008, 319:1096-1100.</ref>. All polyomavirus capsids are constructed from 360 copies of the major coat protein, VP1, arranged in pentamers on a T=7 icosahedral lattice<ref>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.</ref>. 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<ref name=" Tsai B4346 ">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.</ref><ref name=" Low JA1361 ">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.</ref>. Crystal structures are available for complete mPyV particles and for mPyV VP1 pentamers in complex with ganglioside receptor fragments<ref>Stehle T, Yan Y, Benjamin TL, Harrison SC: Structure of murine polyomavirus complexed with an oligosaccharide receptor fragment. Nature 1994, 369:160-163.</ref><ref name=" Stehle T 5139"></ref> as well as for the SV40 VP1 pentamer in complex with GM1 <ref name=" Neu U 5219"></ref>. The glycan-binding properties of the human polyomaviruses are currently being investigated.
+Feng H, Shuda M, Chang Y, Moore PS: Clonal integration of a polyomavirus in human Merkel cell carcinoma. Science 2008, 319:1096-1100.</ref>. All polyomavirus capsids are constructed from 360 copies of the major coat protein, VP1, arranged in pentamers on a T=7 icosahedral lattice<ref>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.</ref>. 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<ref name=" Tsai B4346 ">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.</ref><ref name=" Low JA1361 ">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.</ref>. The glycan-binding properties of the human polyomaviruses are currently being investigated.
 == CFG Participating Investigators contributing to the understanding of this paradigm ==
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 === Structure ===
 A selection of gangliosides is shown below. GM1, GD1a, GD1b and GT1b are used by several polyomaviruses as receptors.

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 === Carbohydrate ligands ===
-<br>
 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<ref name=" Tsai B4346 "></ref>, respectively. The human BK polyomavirus binds to sialylated glycans that include gangliosides GD1b and GT1b <ref name=" Low JA1361 "></ref><ref name=" Dugan AS 14442">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.</ref>.  The human JC polyomavirus uses sialylated glycans<ref>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.</ref><ref>Komagome R, Sawa H, Suzuki T, Suzuki Y, Tanaka S, et al. (2002) Oligosaccharides as receptors for JC virus. J Virol 76: 12992-13000.</ref><ref>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.</ref>as well as the serotonin receptor 5HT<sub>2a</sub>R<ref>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.</ref>as attachment receptors. The receptors for other polyomaviruses, such as the recently identified Merkel Cell Polyomavirus<ref name=" Feng H1096"></ref>, 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<ref name=" Tsai B4346 "></ref><ref name=" Stehle T 5139">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.</ref><ref>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.</ref><ref name=" Neu U 5219">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.</ref><ref> 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.</ref>

← Older revision		Revision as of 17:36, 2 July 2010
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	=== Biosynthesis of ligands ===		=== Biosynthesis of ligands ===

−	~~<br>~~
−	~~Gangliosides, sialylated oligosaccharides are synthesized by the host~~

		+	Gangliosides, sialylated oligosaccharides are synthesized by the host.

	=== Structure ===		=== Structure ===