Source: http://www.asmscience.org/content/book/10.1128/9781555816698.ch11
Timestamp: 2019-04-21 09:05:00+00:00

Document:
The extensive cellular membrane remodeling exerts major effects on cellular metabolic and physiologic functions, which may be important for viral suppression of antiviral responses within the infected host. This chapter describes the current status of our understanding of the induction and formation of membranous viral RNA replication sites for the different picornaviruses. Picornaviruses replicate their genomes in close association with cellular membranes. Fractionation of cytoplasmic extracts from infected cells demonstrated that viral RNA replication activity was associated with these new structures. Subsequently, improved imaging technology greatly increased our knowledge of the morphological changes occurring in cells infected with poliovirus as well as other members of the Picornaviridae family. Picornavirus 3A proteins show a variable size, ranging from 73 to 153 aa. They all contain at least one hydrophobic domain, which most likely serves to anchor the protein in the vesicles at which viral RNA replication takes place. Parechovirus and foot-and-mouth disease virus (FMDV) proteins interact with early secretory pathway membranes, but none of them interacts with GBF1 or interferes with membrane traffic or perturbs the secretory pathway organelle structure. We are now only beginning to understand the details of the three-dimensional structures that ultimately comprise the viral RNA replication complexes and the interactions of viral and cellular factors that lead to the dramatic remodeling of cellular membranes to form these structures. The Picornaviridae are a diverse group of viruses that infect a wide range of hosts; they are responsible for a broad spectrum of disease patterns.
Thin-section electron micrograph of a HeLa cell infected with the Mahoney strain of poliovirus type 1 for 4 h. The cells were fixed and then processed for electron microscopy.
Three-dimensional surface-rendered model of replication complexes observed in poliovirus-infected HeLa cells at 4 h postinfection. Electron tomography was performed on a selected region from a 200-nm-thick section of an infected cell. The model was generated from a tilt series of images digitally processed to produce the reconstruction.
2. Agirre, A.,, A. Barco,, L. Carrasco, and, J. L. Nieva. 2002. Viroporin-mediated membrane permeabilization. Pore formation by nonstructural poliovirus 2B protein. J. Biol. Chem. 277: 40434– 40441.
3. Aldabe, R., and, L. Carrasco. 1995. Induction of membrane proliferation by poliovirus proteins 2C and 2BC. Biochem. Biophys. Res. Commun. 206: 64– 76.
4. Amako, K., and, S. Dales. 1967. Cytopathology of mengovirus infection. II. Proliferation of membranous cisternae. Virology 32: 201– 215.
5. Barco, A., and, L. Carrasco. 1995. A human virus protein, poliovirus protein 2BC, induces membrane proliferation and blocks the exocytic pathway in the yeast Saccharomyces cerevisiae. EMBO J. 14: 3349– 3364.
6. Barton, D. J., and, J. B. Flanegan. 1993. Coupled translation and replication of poliovirus RNA in vitro: synthesis of functional 3D polymerase and infectious virus. J. Virol. 67: 822– 831.
7. Belov, G. A.,, N. Altan-Bonnet,, G. Kovtunovych,, C. L. Jackson,, J. Lippincott-Schwartz, and, E. Ehrenfeld. 2007. Hijacking components of the cellular secretory pathway for replication of poliovirus RNA. J. Virol. 81: 558– 567.
8. Belov, G. A.,, Q. Feng,, K. Nikovics,, C. L. Jackson, and, E. Ehrenfeld. 2008. A critical role of a cellular membrane traffic protein in poliovirus RNA replication. PLoS Pathog. 4: e1000216.
9. Belov, G. A.,, M. H. Fogg, and, E. Ehrenfeld. 2005. Poliovirus proteins induce membrane association of GTPase ADP-ribosylation factor. J. Virol. 79: 7207– 7216.
10. Beske, O.,, M. Reichelt,, M. P. Taylor,, K. Kirkegaard, and, R. Andino. 2007. Poliovirus infection blocks ERGIC-to-Golgi trafficking and induces microtubule-dependent disruption of the Golgi complex. J. Cell Sci. 120: 3207– 3218.
11. Bienz, K.,, D. Egger, and, L. Pasamontes. 1987. Association of polioviral proteins of the P2 genomic region with the viral replication complex and virus-induced membrane synthesis as visualized by electron microscopic immunocytochemistry and autoradiography. Virology 160: 220– 226.
12. Bienz, K.,, D. Egger,, T. Pfister, and, M. Troxler. 1992. Structural and functional characterization of the poliovirus replication complex. J. Virol. 66: 2740– 2747.
13. Bienz, K.,, D. Egger,, Y. Rasser, and, W. Bossart. 1983. Intracellular distribution of poliovirus proteins and the induction of virus-specific cytoplasmic structures. Virology 131: 39– 48.
14. Bienz, K.,, D. Egger,, M. Troxler, and, L. Pasamontes. 1990. Structural organization of poliovirus RNA replication is mediated by viral proteins of the P2 genomic region. J. Virol. 64: 1156– 1163.
15. Brabec-Zaruba, M.,, U. Berka,, D. Blaas, and, R. Fuchs. 2007. Induction of autophagy does not affect human rhinovirus type 2 production. J. Virol. 81: 10815– 10817.
16. Caliguiri, L. A., and, I. Tamm. 1969. Membranous structures associated with translation and transcription of poliovirus RNA. Science 166: 885– 886.
17. Caliguiri, L. A., and, I. Tamm. 1970. The role of cytoplasmic membranes in poliovirus biosynthesis. Virology 42: 100– 111.
18. Campanella, M.,, A. S. de Jong,, K. W. Lanke,, W. J. Melchers,, P. H. Willems,, P. Pinton,, R. Rizzuto, and, F. J. van Kuppeveld. 2004. The coxsackievirus 2B protein suppresses apoptotic host cell responses by manipulating intracellular Ca 2+ homeostasis. J. Biol. Chem. 279: 18440– 18450.
19. Cho, M. W.,, N. Teterina,, D. Egger,, K. Bienz, and, E. Ehrenfeld. 1994. Membrane rearrangement and vesicle induction by recombinant poliovirus 2C and 2BC in human cells. Virology 202: 129– 145.
20. Choe, S. S.,, D. A. Dodd, and, K. Kirkegaard. 2005. Inhibition of cellular protein secretion by picornaviral 3A proteins. Virology 337: 18– 29.
21. Cornell, C. T.,, W. B. Kiosses,, S. Harkins, and, J. L. Whitton. 2007. Coxsackievirus B3 proteins directionally complement each other to downregulate surface major histocompatibility complex class I. J. Virol. 81: 6785– 6797.
22. Cornell, C. T.,, W. B. Kiosses,, S. Harkins, and, J. L. Whitton. 2006. Inhibition of protein trafficking by coxsackievirus B3: multiple viral proteins target a single organelle. J. Virol. 80: 6637– 6647.
23. Cuconati, A.,, A. Molla, and, E. Wimmer. 1998. Brefeldin A inhibits cell-free, de novo synthesis of poliovirus. J. Virol. 72: 6456– 6464.
24. Dales, S.,, H. J. Eggers,, I. Tamm, and, G. E. Palade. 1965. Electron microscopic study of the formation of poliovirus. Virology 26: 379– 389.
25. Dales, S., and, R. M. Franklin. 1962. A comparison of the changes in fine structure of L cells during single cycles of viral multiplication, following their infection with the viruses of Mengo and encephalomyocarditis. J. Cell Biol. 14: 281– 302.
26. Deitz, S. B.,, D. A. Dodd,, S. Cooper,, P. Parham, and, K. Kirkegaard. 2000. MHC I-dependent antigen presentation is inhibited by poliovirus protein 3A. Proc. Natl. Acad. Sci. USA 97: 13790– 13795.
27. de Jong, A. S.,, W. J. Melchers,, D. H. Glaudemans,, P. H. Willems, and, F. J. van Kuppeveld. 2004. Mutational analysis of different regions in the coxsackievirus 2B protein: requirements for homo-multimerization, membrane permeabilization, subcellular localization, and virus replication. J. Biol. Chem. 279: 19924– 19935.
28. de Jong, A. S.,, H. J. Visch,, F. de Mattia,, M. M. van Dommelen,, H. G. Swarts,, T. Luyten,, G. Callewaert,, W. J. Melchers,, P. H. Willems, and, F. J. van Kuppeveld. 2006. The coxsackievirus 2B protein increases efflux of ions from the endoplasmic reticulum and Golgi, thereby inhibiting protein trafficking through the Golgi. J. Biol. Chem. 281: 14144– 14150.
29. de Jong, A. S.,, E. Wessels,, H. B. Dijkman,, J. M. Galama,, W. J. Melchers,, P. H. Willems, and, F. J. van Kuppeveld. 2003. Determinants for membrane association and permeabilization of the coxsackievirus 2B protein and the identification of the Golgi complex as the target organelle. J. Biol. Chem. 278: 1012– 1021.
30. de Jong, A. S.,, F. de Mattia,, M. M. Van Dommelen,, K. Lanke,, W. J. Melchers,, P. H. Willems, and, F. J. van Kuppeveld. 2008. Functional analysis of picornavirus 2B proteins: effects on calcium homeostasis and intracellular protein trafficking. J. Virol. 82: 3782– 3790.
31. Deretic, V., and, B. Levine. 2009. Autophagy, immunity, and microbial adaptations. Cell Host Microbe 5: 527– 549.
32. Dodd, D. A.,, T. H. Giddings, Jr., and, K. Kirkegaard. 2001. Poliovirus 3A protein limits interleukin-6 (IL-6), IL-8, and beta interferon secretion during viral infection. J. Virol. 75: 8158– 8165.
33. Doedens, J.,, L. A. Maynell,, M. W. Klymkowsky, and, K. Kirkegaard. 1994. Secretory pathway function, but not cytoskeletal integrity, is required in poliovirus infection. Arch. Virol. Suppl. 9: 159– 172.
34. Doedens, J. R., and, K. Kirkegaard. 1995. Inhibition of cellular protein secretion by poliovirus proteins 2B and 3A. EMBO J. 14: 894– 907.
35. Echeverri, A. C., and, A. Dasgupta. 1995. Amino terminal regions of poliovirus 2C protein mediate membrane binding. Virology 208: 540– 553.
36. Egger, D., and, K. Bienz. 2005. Intracellular location and trans-location of silent and active poliovirus replication complexes. J. Gen. Virol. 86: 707– 718.
37. Egger, D.,, L. Pasamontes,, R. Bolten,, V. Boyko, and, K. Bienz. 1996. Reversible dissociation of the poliovirus replication complex: functions and interactions of its components in viral RNA synthesis. J. Virol. 70: 8675– 8683.
38. Etchison, D., and, E. Ehrenfeld. 1981. Comparison of replication complexes synthesizing poliovirus RNA. Virology 111: 33– 46.
39. Fogg, M. H.,, N. L. Teterina, and, E. Ehrenfeld. 2003. Membrane requirements for uridylylation of the poliovirus VPg protein and viral RNA synthesis in vitro. J. Virol. 77: 11408– 11416.
40. Friedmann, A., and, H. L. Lipton. 1980. Replication of Theiler’s murine encephalomyelitis viruses in BHK21 cells: an electron microscopic study. Virology 101: 389– 398.
41. Gazina, E. V.,, J. M. Mackenzie,, R. J. Gorrell, and, D. A. Anderson. 2002. Differential requirements for COPI coats in formation of replication complexes among three genera of Picornaviridae. J. Virol. 76: 11113– 11122.
42. Gerber, K.,, E. Wimmer, and, A. V. Paul. 2001. Biochemical and genetic studies of the initiation of human rhinovirus 2 RNA replication: identification of a cis-replicating element in the coding sequence of 2A pro. J. Virol. 75: 10979– 10990.
43. Gorbalenya, A. E.,, V. M. Blinov,, A. P. Donchenko, and, E. V. Koonin. 1989. An NTP-binding motif is the most conserved sequence in a highly diverged monophyletic group of proteins involved in positive strand RNA viral replication. J. Mol. Evol. 28: 256– 268.
44. Gorbalenya, A. E., and, E. V. Koonin. 1989. Viral proteins containing the purine NTP-binding sequence pattern. Nucleic Acids Res. 17: 8413– 8440.
45. Gorbalenya, A. E.,, E. V. Koonin,, A. P. Donchenko, and, V. M. Blinov. 1989. Two related superfamilies of putative helicases involved in replication, recombination, repair and expression of DNA and RNA genomes. Nucleic Acids Res. 17: 4713– 4730.
46. Gosert, R.,, D. Egger, and, K. Bienz. 2000. A cytopathic and a cell culture adapted hepatitis A virus strain differ in cell killing but not in intracellular membrane rearrangements. Virology 266: 157– 169.
47. Guinea, R., and, L. Carrasco. 1991. Effects of fatty acids on lipid synthesis and viral RNA replication in poliovirus-infected cells. Virology 185: 473– 476.
48. Guinea, R., and, L. Carrasco. 1990. Phospholipid biosynthesis and poliovirus genome replication, two coupled phenomena. EMBO J 9: 2011– 2016.
49. Hope, D. A.,, S. E. Diamond, and, K. Kirkegaard. 1997. Genetic dissection of interaction between poliovirus 3D polymerase and viral protein 3AB. J. Virol. 71: 9490– 9498.
50. Huang, S. C.,, C. L. Chang,, P. S. Wang,, Y. Tsai, and, H. S. Liu. 2009. Enterovirus 71-induced autophagy detected in vitro and in vivo promotes viral replication. J. Med. Virol. 81: 1241– 1252.
51. Irurzun, A.,, L. Perez, and, L. Carrasco. 1992. Involvement of membrane traffic in the replication of poliovirus genomes: effects of brefeldin A. Virology 191: 166– 175.
52. Jackson, W. T.,, T. H. Giddings, Jr.,, M. P. Taylor,, S. Mulinyawe,, M. Rabinovitch,, R. R. Kopito, and, K. Kirkegaard. 2005. Subversion of cellular autophagosomal machinery by RNA viruses. PLoS Biol. 3: e156.
53. Kallman, F.,, R. C. Williams,, R. Dulbecco, and, M. Vogt. 1958. Fine structure of changes produced in cultured cells sampled at specified intervals during a single growth cycle of polio virus. J. Biophys. Biochem. Cytol. 4: 301– 308.
54. Kirkegaard, K., and, W. T. Jackson. 2005. Topology of double-membraned vesicles and the opportunity for non-lytic release of cytoplasm. Autophagy 1: 182– 184.
55. Knoops, K.,, M. Kikkert,, S. H. Worm,, J. C. Zevenhoven-Dobbe,, Y. van der Meer,, A. J. Koster,, A. M. Mommaas, and, E. J. Snijder. 2008. SARS-coronavirus replication is supported by a reticulovesicular network of modified endoplasmic reticulum. PLoS Biol. 6: e226.
56. Knox, C.,, K. Moffat,, S. Ali,, M. Ryan, and, T. Wileman. 2005. Foot-and-mouth disease virus replication sites form next to the nucleus and close to the Golgi apparatus, but exclude marker proteins associated with host membrane compartments. J. Gen. Virol. 86: 687– 696.
57. Kondratova, A. A.,, N. Neznanov,, R. V. Kondratov, and, A. V. Gudkov. 2005. Poliovirus protein 3A binds and inactivates LIS1, causing block of membrane protein trafficking and deregulation of cell division. Cell Cycle 4: 1403– 1410.
58. Kopek, B. G.,, G. Perkins,, D. J. Miller,, M. H. Ellisman, and, P. Ahlquist. 2007. Three-dimensional analysis of a viral RNA replication complex reveals a virus-induced mini-organelle. PLoS Biol. 5: e220.
59. Krogerus, C.,, D. Egger,, O. Samuilova,, T. Hyypia, and, K. Bienz. 2003. Replication complex of human parechovirus 1. J. Virol. 77: 8512– 8523.
60. Krogerus, C.,, O. Samuilova,, T. Poyry,, E. Jokitalo, and, T. Hyypia. 2007. Intracellular localization and effects of individually expressed human parechovirus 1 non-structural proteins. J. Gen. Virol. 88: 831– 841.
61. Lama, J.,, A. V. Paul,, K. S. Harris, and, E. Wimmer. 1994. Properties of purified recombinant poliovirus protein 3AB as substrate for viral proteinases and as co-factor for RNA polymerase 3D pol. J. Biol. Chem. 269: 66– 70.
62. Lanke, K. H.,, H. M. van der Schaar,, G. A. Belov,, Q. Feng,, D. Duijsings,, C. L. Jackson,, E. Ehrenfeld, and, F. J. van Kuppeveld. 2009. GBF1, a guanine nucleotide exchange factor for Arf, is crucial for coxsackievirus B3 RNA replication. J. Virol. 83: 11940– 11949.
63. Lawson, M. A., and, B. L. Semler. 1992. Alternate poliovirus nonstructural protein processing cascades generated by primary sites of 3C proteinase cleavage. Virology 191: 309– 320.
64. Lyle, J. M.,, E. Bullitt,, K. Bienz, and, K. Kirkegaard. 2002. Visualization and functional analysis of RNA-dependent RNA polymerase lattices. Science 296: 2218– 2222.
65. Maynell, L. A.,, K. Kirkegaard, and, M. W. Klymkowsky. 1992. Inhibition of poliovirus RNA synthesis by brefeldin A. J. Virol. 66: 1985– 1994.
66. Moffat, K.,, G. Howell,, C. Knox,, G. J. Belsham,, P. Monaghan,, M. D. Ryan, and, T. Wileman. 2005. Effects of foot-and-mouth disease virus nonstructural proteins on the structure and function of the early secretory pathway: 2BC but not 3A blocks endoplasmic reticulum-to-Golgi transport. J. Virol. 79: 4382– 4395.
67. Moffat, K.,, C. Knox,, G. Howell,, S. J. Clark,, H. Yang,, G. J. Belsham,, M. Ryan, and, T. Wileman. 2007. Inhibition of the secretory pathway by foot-and-mouth disease virus 2BC protein is reproduced by coexpression of 2B with 2C, and the site of inhibition is determined by the subcellular location of 2C. J. Virol. 81: 1129– 1139.
68. Molla, A.,, A. V. Paul, and, E. Wimmer. 1991. Cell-free, de novo synthesis of poliovirus. Science 254: 1647– 1651.
69. Molla, A.,, A. V. Paul, and, E. Wimmer. 1993. Effects of temperature and lipophilic agents on poliovirus formation and RNA synthesis in a cell-free system. J. Virol. 67: 5932– 5938.
70. Monaghan, P.,, H. Cook,, T. Jackson,, M. Ryan, and, T. Wileman. 2004. The ultrastructure of the developing replication site in foot-and-mouth disease virus-infected BHK-38 cells. J. Gen. Virol. 85: 933– 946.
71. Mosser, A. G.,, L. A. Caliguiri, and, I. Tamm. 1972. Incorporation of lipid precursors into cytoplasmic membranes of poliovirus-infected HeLa cells. Virology 47: 39– 47.
72. Mossessova, E.,, R. A. Corpina, and, J. Goldberg. 2003. Crystal structure of ARF1*Sec7 complexed with Brefeldin A and its implications for the guanine nucleotide exchange mechanism. Mol. Cell 12: 1403– 1411.
73. Nayak, A.,, I. G. Goodfellow, and, G. J. Belsham. 2005. Factors required for the uridylylation of the foot-and-mouth disease virus 3B1, 3B2, and 3B3 peptides by the RNA-dependent RNA polymerase (3D pol) in vitro. J. Virol. 79: 7698– 7706.
74. Neufeld, K. L.,, O. C. Richards, and, E. Ehrenfeld. 1991. Purification, characterization, and comparison of poliovirus RNA polymerase from native and recombinant sources. J. Biol. Chem. 266: 24212– 24219.
75. Neznanov, N.,, K. P. Chumakov,, A. Ullrich,, V. I. Agol, and, A. V. Gudkov. 2002. Unstable receptors disappear from cell surface during poliovirus infection. Med. Sci. Monit. 8: BR391– BR396.
76. Neznanov, N.,, A. Kondratova,, K. M. Chumakov,, B. Angres,, B. Zhumabayeva,, V. I. Agol, and, A. V. Gudkov. 2001. Poliovirus protein 3A inhibits tumor necrosis factor (TNF)-induced apoptosis by eliminating the TNF receptor from the cell surface. J. Virol. 75: 10409– 10420.
77. Nieva, J. L.,, A. Agirre,, S. Nir, and, L. Carrasco. 2003. Mechanisms of membrane permeabilization by picornavirus 2B viroporin. FEBS Lett. 552: 68– 73.
78. O’Donnell, V. K.,, J. M. Pacheco,, T. M. Henry, and, P. W. Mason. 2001. Subcellular distribution of the foot-and-mouth disease virus 3A protein in cells infected with viruses encoding wild-type and bovine-attenuated forms of 3A. Virology 287: 151– 162.
79. Paul, A. V.,, A. Molla, and, E. Wimmer. 1994. Studies of a putative amphipathic helix in the N-terminus of poliovirus protein 2C. Virology 199: 188– 199.
80. Paul, A. V.,, E. Rieder,, D. W. Kim,, J. H. van Boom, and, E. Wimmer. 2000. Identification of an RNA hairpin in poliovirus RNA that serves as the primary template in the in vitro uridylylation of VPg. J. Virol. 74: 10359– 10370.
81. Paul, A. V.,, J. H. van Boom,, D. Filippov, and, E. Wimmer. 1998. Protein-primed RNA synthesis by purified poliovirus RNA polymerase. Nature 393: 280– 284.
82. Pelham, H. R. 1978. Translation of encephalomyocarditis virus RNA in vitro yields an active proteolytic processing enzyme. Eur. J. Biochem. 85: 457– 462.
83. Penman, S. 1965. Stimulation of the incorporation of choline in poliovirus-infected cells. Virology 25: 149– 152.
84. Pfister, T.,, K. W. Jones, and, E. Wimmer. 2000. A cysteine-rich motif in poliovirus protein 2C ATPase is involved in RNA replication and binds zinc in vitro. J. Virol. 74: 334– 343.
85. Rust, R. C.,, L. Landmann,, R. Gosert,, B. L. Tang,, W. Hong,, H. P. Hauri,, D. Egger, and, K. Bienz. 2001. Cellular COPII proteins are involved in production of the vesicles that form the poliovirus replication complex. J. Virol. 75: 9808– 9818.
86. Samuilova, O.,, C. Krogerus,, I. Fabrichniy, and, T. Hyypia. 2006. ATP hydrolysis and AMP kinase activities of nonstructural protein 2C of human parechovirus 1. J. Virol. 80: 1053– 1058.
87. Schimmel, H., and, P. Traub. 1987. The effect of mengovirus infection on lipid synthesis in cultured Ehrlich ascites tumor cells. Lipids 22: 95– 103.
88. Schlegel, A.,, T. H. Giddings, Jr.,, M. S. Ladinsky, and, K. Kirkegaard. 1996. Cellular origin and ultrastructure of membranes induced during poliovirus infection. J. Virol. 70: 6576– 6588.
89. Skinner, M. S.,, S. Halperen, and, J. C. Harkin. 1968. Cytoplasmic membrane-bound vesicles in echovirus 12-infected cells. Virology 36: 241– 253.
90. Suhy, D. A.,, T. H. Giddings, Jr., and, K. Kirkegaard. 2000. Remodeling the endoplasmic reticulum by poliovirus infection and by individual viral proteins: an autophagy-like origin for virus-induced vesicles. J. Virol. 74: 8953– 8965.
91. Takegami, T.,, R. J. Kuhn,, C. W. Anderson, and, E. Wimmer. 1983. Membrane-dependent uridylylation of the genome-linked protein VPg of poliovirus. Proc. Natl. Acad. Sci. USA 80: 7447– 7451.
92. Tang, W. F.,, S. Y. Yang,, B. W. Wu,, J. R. Jheng,, Y. L. Chen,, C. H. Shih,, K. H. Lin,, H. C. Lai,, P. Tang, and, J. T. Horng. 2007. Reticulon 3 binds the 2C protein of enterovirus 71 and is required for viral replication. J. Biol. Chem. 282: 5888– 5898.
93. Taylor, M. P.,, T. B. Burgon,, K. Kirkegaard, and, W. T. Jackson. 2009. Role of microtubules in extracellular release of poliovirus. J. Virol. 83: 6599– 6609.
94. Taylor, M. P., and, K. Kirkegaard. 2007. Modification of cellular autophagy protein LC3 by poliovirus. J. Virol. 81: 12543– 12553.
95. Taylor, M. P., and, K. Kirkegaard. 2008. Potential subversion of autophagosomal pathway by picornaviruses. Autophagy 4: 286– 289.
96. Teterina, N. L.,, D. Egger,, K. Bienz,, D. M. Brown,, B. L. Semler, and, E. Ehrenfeld. 2001. Requirements for assembly of poliovirus replication complexes and negative-strand RNA synthesis. J. Virol. 75: 3841– 3850.
97. Teterina, N. L.,, A. E. Gorbalenya,, D. Egger,, K. Bienz, and, E. Ehrenfeld. 1997. Poliovirus 2C protein determinants of membrane binding and rearrangements in mammalian cells. J. Virol. 71: 8962– 8972.
98. Tolskaya, E. A.,, L. I. Romanova,, M. S. Kolesnikova,, A. P. Gmyl,, A. E. Gorbalenya, and, V. I. Agol. 1994. Genetic studies on the poliovirus 2C protein, an NTPase. A plausible mechanism of guanidine effect on the 2C function and evidence for the importance of 2C oligomerization. J. Mol. Biol. 236: 1310– 1323.
99. Van Dyke, T. A.,, R. J. Rickles, and, J. B. Flanegan. 1982. Genome-length copies of poliovirion RNA are synthesized in vitro by the poliovirus RNA-dependent RNA polymerase. J. Biol. Chem. 257: 4610– 4617.
100. van Kuppeveld, F. J.,, A. S. de Jong,, W. J. Melchers, and, P. H. Willems. 2005. Enterovirus protein 2B po(u)res out the calcium: a viral strategy to survive? Trends Microbiol. 13: 41– 44.
101. van Kuppeveld, F. J.,, J. M. Galama,, J. Zoll, and, W. J. Melchers. 1995. Genetic analysis of a hydrophobic domain of coxsackie B3 virus protein 2B: a moderate degree of hydrophobicity is required for a cis-acting function in viral RNA synthesis. J. Virol. 69: 7782– 7790.
102. van Kuppeveld, F. J.,, J. M. Galama,, J. Zoll,, P. J. van den Hurk, and, W. J. Melchers. 1996. Coxsackie B3 virus protein 2B contains cationic amphipathic helix that is required for viral RNA replication. J. Virol. 70: 3876– 3886.
103. Vartapetian, A. B.,, E. V. Koonin,, V. I. Agol, and, A. A. Bogdanov. 1984. Encephalomyocarditis virus RNA synthesis in vitro is protein-primed. EMBO J 3: 2593– 2598.
105. Welsch, S.,, S. Miller,, I. Romero-Brey,, A. Merz,, C. K. Bleck,, P. Walther,, S. D. Fuller,, C. Antony,, J. Krijnse-Locker, and, R. Bartenschlager. 2009. Composition and three-dimensional architecture of the dengue virus replication and assembly sites. Cell Host Microbe 5: 365– 375.
106. Wessels, E.,, D. Duijsings,, K. H. Lanke,, W. J. Melchers,, C. L. Jackson, and, F. J. van Kuppeveld. 2007. Molecular determinants of the interaction between coxsackievirus protein 3A and guanine nucleotide exchange factor GBF1. J. Virol. 81: 5238– 5245.
107. Wessels, E.,, D. Duijsings,, K. H. Lanke,, S. H. van Dooren,, C. L. Jackson,, W. J. Melchers, and, F. J. van Kuppeveld. 2006. Effects of picornavirus 3A proteins on protein transport and GBF1-dependent COP-I recruitment. J. Virol. 80: 11852– 11860.
108. Wessels, E.,, D. Duijsings,, T. K. Niu,, S. Neumann,, V. M. Oorschot,, F. de Lange,, K. H. Lanke,, J. Klumperman,, A. Henke,, C. L. Jackson,, W. J. Melchers, and, F. J. van Kuppeveld. 2006. A viral protein that blocks Arf1-mediated COP-I assembly by inhibiting the guanine nucleotide exchange factor GBF1. Dev. Cell 11: 191– 201.
109. Wessels, E.,, D. Duijsings,, R. A. Notebaart,, W. J. Melchers, and, F. J. van Kuppeveld. 2005. A proline-rich region in the coxsackievirus 3A protein is required for the protein to inhibit endoplasmic reticulum-to-Golgi transport. J. Virol. 79: 5163– 5173.
110. Wong, J.,, J. Zhang,, X. Si,, G. Gao,, I. Mao,, B. M. McManus, and, H. Luo. 2008. Autophagosome supports coxsackievirus B3 replication in host cells. J. Virol. 82: 9143– 9153.
111. Yoon, S. Y.,, Y. E. Ha,, J. E. Choi,, J. Ahn,, H. Lee,, H. S. Kweon,, J. Y. Lee, and, D. H. Kim. 2008. Coxsackievirus B4 uses autophagy for replication after calpain activation in rat primary neurons. J. Virol. 82: 11976– 11978.

References: in fine
 V. 
 V. 
 V. 
 V. 
 V. 
 V. 
 V. 
 V. 
 V. 
 V. 
 V. 
 V. 
 V. 
 V. 
 V. 
 V. 
 V. 
 V. 
 V. 
 V. 
 V.