Reovirus hemagglutinin (sigma 1)

From CFGparadigms

(Difference between revisions)
Jump to: navigation, search
Line 1: Line 1:
-
Mammalian orthoreoviruses (reoviruses) are useful models for studies of viral receptor recognition and the pathogenesis of viral disease. Reovirus also efficiently lyses tumor cells in experimental animals (Duncan et al., 1978; Coffey et al., 1998)<ref>Duncan, M.R., Stanish, S.M., and Cox, D.C. Differential sensitivity of normal and transformed human  
+
Mammalian orthoreoviruses (reoviruses) are useful models for studies of viral receptor recognition and the pathogenesis of viral disease. Reovirus also efficiently lyses tumor cells in experimental animals<ref>Duncan, M.R., Stanish, S.M., and Cox, D.C. Differential sensitivity of normal and transformed human cells to reovirus infection. J. Virol. 28:444-449, 1978.</ref><ref> Coffey, M.C., Strong, J.E., Forsyth, P.A., and Lee, P.W. Reovirus therapy of tumors with activated Ras pathway. Science 282:1332-1334, 1998.</ref> and has shown efficacy in clinical trials for aggressive and refractory human tumors<ref>Stoeckel, J., and Hay, J.G. Drug evaluation: Reolysin--wild-type reovirus as a cancer therapeutic. Curr. Opin. Mol. Ther. 8:249-260, 2006.</ref><ref>Twigger, K., Vidal, L., White, C.L., De Bono, J.S., Bhide, S., Coffey, M., Thompson, B., Vile, R.G., Heinemann, L., Pandha, H.S., et al. Enhanced in vitro and in vivo cytotoxicity of combined reovirus and radiotherapy. Clin. Cancer Res. 14:912-923, 2008. </ref>. Reovirus forms double-shelled particles<ref>Dryden, K.A., Wang, G., Yeager, M., Nibert, M.L., Coombs, K.M., Furlong, D.B., Fields, B.N., and Baker, T.S. Early steps in reovirus infection are associated with dramatic changes in supramolecular structure and protein conformation: analysis of virions and subviral particles by cryoelectron microscopy and image reconstruction. J. Cell Biol. 122:1023-1041, 1993.</ref> that contain a segmented dsRNA genome. The reovirus sigma 1 protein is a long, fiber-like molecule that extends from the virion surface<ref>Furlong, D.B., Nibert, M.L., and Fields, B.N. Sigma 1 protein of mammalian reoviruses extends from the surfaces of viral particles. J. Virol. 62:246-256, 1988.</ref> and mediates viral attachment<ref>Weiner, H.L., Ault, K.A., and Fields, B.N. Interaction of reovirus with cell surface receptors. I. Murine and human lymphocytes have a receptor for the hemagglutinin of reovirus type 3. J. Immunol. 124:2143-2148, 1980.</ref><ref>Lee, P.W.K., Hayes, E.C., and Joklik, W.K. Protein σ1 is the reovirus cell attachment protein. Virology 108:156-163, 1981.</ref>. The three human serotypes (T1, T2, and T3) differ in cellular tropism, which correlates directly with receptor-binding properties of sigma 1. Sialic acid serves as an essential receptor for T3 reovirus on murine erythroleukemia (MEL) cells<ref>Rubin, D.H., Wetzel, J.D., Williams, W.V., Cohen, J.A., Dworkin, C., and Dermody, T.S. Binding of type 3 reovirus by a domain of the σ1 protein important for hemagglutination leads to infection of murine erythroleukemia cells. J. Clin. Invest. 90:2536-2542, 1992.</ref>, and it functions as a coreceptor on murine L929 (L) cells<ref>Gentsch, J.R., and Pacitti, A.F. Effect of neuraminidase treatment of cells and effect of soluble glycoproteins on type 3 reovirus attachment to murine L cells. J. Virol. 56:356-364, 1985.</ref><ref>Pacitti, A., and Gentsch, J.R. Inhibition of reovirus type 3 binding to host cells by sialylated glycoproteins is mediated through the viral attachment protein. J. Virol. 61:1407-1415, 1987. </ref><ref>Paul, R.W., Choi, A.H., and Lee, P.W.K. The α-anomeric form of sialic acid is the minimal receptor determinant recognized by reovirus. Virology 172:382-385, 1989.</ref><ref>Rubin, D.H., Wetzel, J.D., Williams, W.V., Cohen, J.A., Dworkin, C., and Dermody, T.S. Binding of type 3 reovirus by a domain of the σ1 protein important for hemagglutimurine erythroleukemia cells. J. Clin. Invest. 90:2536-2542, 1992.</ref><ref>Nibert, M.L., Chappell, J.D., and Dermody, T.S. Infectious subvirion particles of reovirus type 3 Dearing exhibit a loss in infectivity and contain a cleaved σ1 protein. J. Virol. 69:5057-5067, 1995.</ref>. Residues involved in sialic acid-binding map to the center of the long fiber, close to the midpoint of the molecule<ref>Chappell, J.D., Prota, A., Dermody, T.S., and Stehle, T. Crystal structure of reovirus attachment protein σ1 reveals evolutionary relationship to adenovirus fiber. EMBO J. 21:1-11, 2002.</ref>, in a repetitive structural region known as the triple β-spiral. The T1 sigma 1 protein binds to cell-surface glycans of unknown structure.
-
cells to reovirus infection. J. Virol. 28:444-449, 1978.</ref><ref> Coffey, M.C., Strong, J.E., Forsyth, P.A., and Lee, P.W. Reovirus therapy of tumors with activated Ras  
+
-
pathway. Science 282:1332-1334, 1998.</ref> and has shown efficacy in clinical trials for aggressive and refractory human tumors (Stoeckel & Hay, 2006; Twigger et al., 2008)<ref>Stoeckel, J., and Hay, J.G. Drug evaluation: Reolysin--wild-type reovirus as a cancer therapeutic. Curr. Opin. Mol. Ther. 8:249-260, 2006.</ref><ref>Twigger, K., Vidal, L., White, C.L., De Bono, J.S., Bhide, S., Coffey, M., Thompson, B., Vile, R.G., Heinemann, L., Pandha, H.S., et al. Enhanced in vitro and in vivo cytotoxicity of combined reovirus and radiotherapy. Clin. Cancer Res. 14:912-923, 2008. </ref>. Reovirus forms double-shelled particles (Dryden et al., 1993)<ref>Dryden, K.A., Wang, G., Yeager, M., Nibert, M.L., Coombs, K.M., Furlong, D.B., Fields, B.N., and Baker, T.S. Early steps in reovirus infection are associated with dramatic changes in supramolecular structure and protein conformation: analysis of virions and subviral particles by cryoelectron microscopy and image reconstruction. J. Cell Biol. 122:1023-1041, 1993.</ref> that contain a segmented dsRNA genome. The reovirus sigma 1 protein is a long, fiber-like molecule that extends from the virion surface (Furlong et al., 1988)<ref>Furlong, D.B., Nibert, M.L., and Fields, B.N. Sigma 1 protein of mammalian reoviruses extends from the surfaces of viral particles. J. Virol. 62:246-256, 1988.</ref> and mediates viral attachment (Weiner et al., 1980; Lee et al., 1981)<ref></ref><ref></ref>. The three human serotypes (T1, T2, and T3) differ in cellular tropism, which correlates directly with receptor-binding properties of sigma 1. Sialic acid serves as an essential receptor for T3 reovirus on murine erythroleukemia (MEL) cells (Rubin et al., 1992; Chappell et al., 1997)<ref></ref><ref></ref>, and it functions as a coreceptor on murine L929 (L) cells (Gentsch & Pacitti, 1985; Pacitti & Gentsch, 1987; Paul et al., 1989; Rubin et al., 1992; Nibert et al., 1995)<ref></ref><ref></ref><ref></ref><ref></ref><ref></ref>. Residues involved in sialic acid-binding map to the center of the long fiber, close to the midpoint of the molecule (Chappell et al., 2002)<ref></ref>, in a repetitive structural region known as the triple β-spiral. The T1 sigma 1 protein binds to cell-surface glycans of unknown structure.
+
-
The triple β-spiral of sigma 1 functions as a trimerization domain and defines a novel carbohydrate-recognition motif. Other carbohydrate-recognition domains, such as those of the C-type lectin superfamily (Weis et al.,1998)<ref></ref> or the sialic acid-binding domains in the Siglec family of adhesion proteins (Crocker & Varki, 2001)<ref></ref>, have been described, but none are formed by a repetitive, fiber-like structure such as the one present in sigma 1. In fact, the domain in sigma 1 that binds sialic acid constitutes a carbohydrate-binding “cassette” that could be endowed with altered ligand-binding properties or grafted onto other trimeric structures and used to create avidity for carbohydrates. For example, the adenovirus fiber shaft could be licensed with sialic acid-binding capacity using this approach. These properties render the sigma 1 protein unique among the structurally known glycan-binding moieties.
+
The triple β-spiral of sigma 1 functions as a trimerization domain and defines a novel carbohydrate-recognition motif. Other carbohydrate-recognition domains, such as those of the C-type lectin superfamily<ref>Weis, W.I., Taylor, M.E., and Drickamer, K. The C-type lectin superfamily in the immune system. Immunol. Rev. 163:19-34, 1998.</ref> or the sialic acid-binding domains in the Siglec family of adhesion proteins<ref>Crocker, P.R., and Varki, A. Siglecs in the immune system. Immunology 103:137-145, 2001.</ref>(see [http://glycobank.mit.edu/glycoWiki/Main_Page Siglec paradigms]), have been described, but none are formed by a repetitive, fiber-like structure such as the one present in sigma 1. In fact, the domain in sigma 1 that binds sialic acid constitutes a carbohydrate-binding “cassette” that could be endowed with altered ligand-binding properties or grafted onto other trimeric structures and used to create avidity for carbohydrates. For example, the adenovirus fiber shaft could be licensed with sialic acid-binding capacity using this approach. These properties render the sigma 1 protein unique among the structurally known glycan-binding moieties.
== CFG Participating Investigators contributing to the understanding of this paradigm ==
== CFG Participating Investigators contributing to the understanding of this paradigm ==
Line 38: Line 36:
<br>
<br>
== Related GBPs ==
== Related GBPs ==
-
The attachment protein of adenovirus, fiber, is a structural homolog of sigma 1. At least one adenovirus serotype (Ad37) is known to bind glycan receptors via residues in the fiber protein (Burmeister et al., 2004)<ref></ref>. The actual binding site is not homologous. However, information about reovirus glycan binding could also be used to engineer adenovirus fiber proteins (or other trimeric fiber-like proteins) that possess novel glycan-binding properties.
+
The attachment protein of adenovirus, fiber, is a structural homolog of sigma 1. At least one adenovirus serotype (Ad37) is known to bind glycan receptors via residues in the fiber protein<ref>Burmeister WP, Guilligay D, Cusack S, Wadell G, Arnberg N: Crystal structure of species D adenovirus fiber knobs and their sialic acid binding sites. Journal of Virology 2004, 78:7727-7736.</ref>. The actual binding site is not homologous. However, information about reovirus glycan binding could also be used to engineer adenovirus fiber proteins (or other trimeric fiber-like proteins) that possess novel glycan-binding properties.
== References ==
== References ==

Revision as of 21:16, 9 April 2010

Mammalian orthoreoviruses (reoviruses) are useful models for studies of viral receptor recognition and the pathogenesis of viral disease. Reovirus also efficiently lyses tumor cells in experimental animals[1][2] and has shown efficacy in clinical trials for aggressive and refractory human tumors[3][4]. Reovirus forms double-shelled particles[5] that contain a segmented dsRNA genome. The reovirus sigma 1 protein is a long, fiber-like molecule that extends from the virion surface[6] and mediates viral attachment[7][8]. The three human serotypes (T1, T2, and T3) differ in cellular tropism, which correlates directly with receptor-binding properties of sigma 1. Sialic acid serves as an essential receptor for T3 reovirus on murine erythroleukemia (MEL) cells[9], and it functions as a coreceptor on murine L929 (L) cells[10][11][12][13][14]. Residues involved in sialic acid-binding map to the center of the long fiber, close to the midpoint of the molecule[15], in a repetitive structural region known as the triple β-spiral. The T1 sigma 1 protein binds to cell-surface glycans of unknown structure.

The triple β-spiral of sigma 1 functions as a trimerization domain and defines a novel carbohydrate-recognition motif. Other carbohydrate-recognition domains, such as those of the C-type lectin superfamily[16] or the sialic acid-binding domains in the Siglec family of adhesion proteins[17](see Siglec paradigms), have been described, but none are formed by a repetitive, fiber-like structure such as the one present in sigma 1. In fact, the domain in sigma 1 that binds sialic acid constitutes a carbohydrate-binding “cassette” that could be endowed with altered ligand-binding properties or grafted onto other trimeric structures and used to create avidity for carbohydrates. For example, the adenovirus fiber shaft could be licensed with sialic acid-binding capacity using this approach. These properties render the sigma 1 protein unique among the structurally known glycan-binding moieties.

Contents

CFG Participating Investigators contributing to the understanding of this paradigm

CFG Participating Investigators (PIs) contributing to the understanding of sigma 1 include: Terence Dermody, Thilo Stehle

Progress toward understanding this GBP paradigm

Carbohydrate ligands


Cellular expression


Structure


Biological roles of GBP-ligand interaction


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 "reovirus".

Glycan profiling


Glycogene microarray


Knockout mouse lines


Glycan array


Related GBPs

The attachment protein of adenovirus, fiber, is a structural homolog of sigma 1. At least one adenovirus serotype (Ad37) is known to bind glycan receptors via residues in the fiber protein[18]. The actual binding site is not homologous. However, information about reovirus glycan binding could also be used to engineer adenovirus fiber proteins (or other trimeric fiber-like proteins) that possess novel glycan-binding properties.

References

  1. Duncan, M.R., Stanish, S.M., and Cox, D.C. Differential sensitivity of normal and transformed human cells to reovirus infection. J. Virol. 28:444-449, 1978.
  2. Coffey, M.C., Strong, J.E., Forsyth, P.A., and Lee, P.W. Reovirus therapy of tumors with activated Ras pathway. Science 282:1332-1334, 1998.
  3. Stoeckel, J., and Hay, J.G. Drug evaluation: Reolysin--wild-type reovirus as a cancer therapeutic. Curr. Opin. Mol. Ther. 8:249-260, 2006.
  4. Twigger, K., Vidal, L., White, C.L., De Bono, J.S., Bhide, S., Coffey, M., Thompson, B., Vile, R.G., Heinemann, L., Pandha, H.S., et al. Enhanced in vitro and in vivo cytotoxicity of combined reovirus and radiotherapy. Clin. Cancer Res. 14:912-923, 2008.
  5. Dryden, K.A., Wang, G., Yeager, M., Nibert, M.L., Coombs, K.M., Furlong, D.B., Fields, B.N., and Baker, T.S. Early steps in reovirus infection are associated with dramatic changes in supramolecular structure and protein conformation: analysis of virions and subviral particles by cryoelectron microscopy and image reconstruction. J. Cell Biol. 122:1023-1041, 1993.
  6. Furlong, D.B., Nibert, M.L., and Fields, B.N. Sigma 1 protein of mammalian reoviruses extends from the surfaces of viral particles. J. Virol. 62:246-256, 1988.
  7. Weiner, H.L., Ault, K.A., and Fields, B.N. Interaction of reovirus with cell surface receptors. I. Murine and human lymphocytes have a receptor for the hemagglutinin of reovirus type 3. J. Immunol. 124:2143-2148, 1980.
  8. Lee, P.W.K., Hayes, E.C., and Joklik, W.K. Protein σ1 is the reovirus cell attachment protein. Virology 108:156-163, 1981.
  9. Rubin, D.H., Wetzel, J.D., Williams, W.V., Cohen, J.A., Dworkin, C., and Dermody, T.S. Binding of type 3 reovirus by a domain of the σ1 protein important for hemagglutination leads to infection of murine erythroleukemia cells. J. Clin. Invest. 90:2536-2542, 1992.
  10. Gentsch, J.R., and Pacitti, A.F. Effect of neuraminidase treatment of cells and effect of soluble glycoproteins on type 3 reovirus attachment to murine L cells. J. Virol. 56:356-364, 1985.
  11. Pacitti, A., and Gentsch, J.R. Inhibition of reovirus type 3 binding to host cells by sialylated glycoproteins is mediated through the viral attachment protein. J. Virol. 61:1407-1415, 1987.
  12. Paul, R.W., Choi, A.H., and Lee, P.W.K. The α-anomeric form of sialic acid is the minimal receptor determinant recognized by reovirus. Virology 172:382-385, 1989.
  13. Rubin, D.H., Wetzel, J.D., Williams, W.V., Cohen, J.A., Dworkin, C., and Dermody, T.S. Binding of type 3 reovirus by a domain of the σ1 protein important for hemagglutimurine erythroleukemia cells. J. Clin. Invest. 90:2536-2542, 1992.
  14. Nibert, M.L., Chappell, J.D., and Dermody, T.S. Infectious subvirion particles of reovirus type 3 Dearing exhibit a loss in infectivity and contain a cleaved σ1 protein. J. Virol. 69:5057-5067, 1995.
  15. Chappell, J.D., Prota, A., Dermody, T.S., and Stehle, T. Crystal structure of reovirus attachment protein σ1 reveals evolutionary relationship to adenovirus fiber. EMBO J. 21:1-11, 2002.
  16. Weis, W.I., Taylor, M.E., and Drickamer, K. The C-type lectin superfamily in the immune system. Immunol. Rev. 163:19-34, 1998.
  17. Crocker, P.R., and Varki, A. Siglecs in the immune system. Immunology 103:137-145, 2001.
  18. Burmeister WP, Guilligay D, Cusack S, Wadell G, Arnberg N: Crystal structure of species D adenovirus fiber knobs and their sialic acid binding sites. Journal of Virology 2004, 78:7727-7736.

Acknowledgements

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

Personal tools