Chapter 8 : Genome Replication II: the Process

MyBook is a cheap paperback edition of the original book and will be sold at uniform, low price.

Preview this chapter:
Zoom in

Genome Replication II: the Process, Page 1 of 2

| /docserver/preview/fulltext/10.1128/9781555816698/9781555816032_Chap08-1.gif /docserver/preview/fulltext/10.1128/9781555816698/9781555816032_Chap08-2.gif


In this chapter the authors attempt to dissect the mechanisms that underlie picornavirus RNA replication by first addressing how the viral template RNA may be specifically recognized. They then discuss the coordination of viral translation with negative-strand RNA synthesis. This discussion is followed by a description of the organization of proteins in the RNA replication complex on two-dimensional membrane surfaces, with an emphasis on viral proteins that rearrange cytoplasmic membrane structures and tether RNA replication complexes to the rearranged membranous vesicles as well as viral polymerase proteins and the proteins with which they interact. Then, the chapter describes how the cascade of proteolytic processing contributes to the formation and maturation of picornavirus RNA replication complexes. Finally, steps in the synthesis and utilization of the protein-nucleotidyl primer for initiation of picornavirus RNA synthesis are presented as a lead-in to a discussion of RNA chain elongation and the topology of the RNA in the viral RNA replication complex. Given the unique viral protein-protein and protein-RNA interfaces highlighted in the processes, picornavirus RNA replication remains an attractive target for the development of small-molecule inhibitors that disrupt this crucial part of the viral replication cycle.

Citation: Kirkegaard K, Semler B. 2010. Genome Replication II: the Process, p 127-140. In Ehrenfeld E, Domingo E, Roos R (ed), The Picornaviruses. ASM Press, Washington, DC. doi: 10.1128/9781555816698.ch8
Highlighted Text: Show | Hide
Loading full text...

Full text loading...


Image of Figure 1.
Figure 1.

Ways to achieve tethering of a newly synthesized protein to its mRNA. (A) RNA display. Short RNAs with randomized regions were translated in vitro. When the sequence is engineered so that the last amino acid is unique, and present in the mixture as a puromycin derivative, the newly synthesized polypeptide can become covalently attached to the RNA. Then, selection for the functions of the peptide also selects for its “recipe,” to which it is covalently bound. The illustration was adapted from reference with permission of the publisher. (B) Model for the requirement for translation in for an approximately 7,500-nucleotide picornavirus positive-strand RNA to assemble into an RNA replication complex. Certain newly synthesized proteins display high nonspecific binding affinities both for RNA and for membranes. As a consequence, the mRNA that encodes the new proteins is brought to the target membranes with them. (Modified from reference .)

Citation: Kirkegaard K, Semler B. 2010. Genome Replication II: the Process, p 127-140. In Ehrenfeld E, Domingo E, Roos R (ed), The Picornaviruses. ASM Press, Washington, DC. doi: 10.1128/9781555816698.ch8
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of Figure 2.
Figure 2.

Polymerase-VPg complexes. (A) UMP-VPg-binding site at the polymerase active site, as seen in the cocrystal with FMDV polymerase and FMDV VPg in the presence of UTP. (B) VPg-binding site on the “back” of the polymerase, as seen in the cocrystal of CVB3 polymerase bound to CVB3-encoded VPg in the absence of UTP. (Panels A and B were modified from illustrations published in reference .) (C) The locations of the two VPg-binding sites on an assemblage of poliovirus polymerase molecules interacting along Interface I; as neither of these complexes has been observed structurally for poliovirus, the locations are indicated with shaded circles. (Modified from reference .) T, thumb contacts of Interface I; P, palm contacts of Interface I.

Citation: Kirkegaard K, Semler B. 2010. Genome Replication II: the Process, p 127-140. In Ehrenfeld E, Domingo E, Roos R (ed), The Picornaviruses. ASM Press, Washington, DC. doi: 10.1128/9781555816698.ch8
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of Figure 3.
Figure 3.

Replication of double-stranded and single-stranded templates with immobilized replication complexes. (A) Movement of a double-stranded template past an immobilized, tracking replication complex (vertical column) creates positive supercoils in front of the replication fork and negative supercoils behind it. These can only be relaxed by free rotation of the ends (marked with asterisks) or by breaking one of the single strands, as with a nuclease (which would leave a nick or a break), a combination of a nuclease and a ligase, or a topoisomerase. (Modified from reference with permission from the publisher.) (B) Movement of single-stranded templates along immobilized replication complexes does not present topological problems but does require movement of the template and primer strands and some mechanism to prevent their stable annealing.

Citation: Kirkegaard K, Semler B. 2010. Genome Replication II: the Process, p 127-140. In Ehrenfeld E, Domingo E, Roos R (ed), The Picornaviruses. ASM Press, Washington, DC. doi: 10.1128/9781555816698.ch8
Permissions and Reprints Request Permissions
Download as Powerpoint


1. Adams, P.,, E. Kandiah,, G. Effantin,, A. C. Steven, and, E. Ehrenfeld. 2009. Poliovirus 2C protein forms homo-oligomeric structures required for ATPase activity. J. Biol. Chem. 284: 2201222021.
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: 4043440441.
3. Amero, C. D.,, J. J. Arnold,, I. M. Moustafa,, C. E. Cameron, and, M. P. Foster. 2008. Identification of the oriI-binding site of poliovirus 3C protein by nuclear magnetic resonance spectroscopy. J. Virol. 82: 43634370.
4. Andino, R.,, G. E. Rieckhof,, P. L. Achacoso, and, D. Baltimore. 1993. Poliovirus RNA synthesis utilizes an RNP complex formed around the 5′-end of viral RNA. EMBO J. 12: 35873598.
5. Back, S. H.,, Y. K. Kim,, W. J. Kim,, S. Cho,, H. R. Oh,, J. E. Kim, and, S. K. Jang. 2002. Translation of polioviral mRNA is inhibited by cleavage of polypyrimidine tract-binding proteins executed by polioviral 3C pro. J. Virol. 76: 25292542.
6. Barton, D. J.,, B. J. Morasco, and, J. B. Flanegan. 1999. Translating ribosomes inhibit poliovirus negative-strand RNA synthesis. J. Virol. 73: 1010410112.
7. Barton, D. J.,, B. J. O’Donnell, and, J. B. Flanegan. 2001. 5′ cloverleaf in poliovirus RNA is a cis-acting replication element required for negative-strand synthesis. EMBO J. 20: 14391448.
8. Beckman, M. T., and, K. Kirkegaard. 1998. Site size of cooperative single-stranded RNA binding by poliovirus RNA-dependent RNA polymerase. J. Biol. Chem. 273: 67246730.
9. Bishop, J. M.,, G. Koch,, B. Evans, and, M. Merriman. 1969. Poliovirus replicative intermediate: structural basis of infectivity. J. Mol. Biol. 46: 235249.
10. Blumenthal, T., and, G. G. Carmichael. 1979. RNA replication: function and structure of Qβ-replicase. Annu. Rev. Biochem. 48: 525548.
11. Burgon, T. B.,, J. A. Jenkins,, S. B. Deitz,, J. F. Spagnolo, and, K. Kirkegaard. 2009. Bypass suppression of small-plaque pheno-types by a mutation in poliovirus 2A that enhances apoptosis. J. Virol. 83: 1012910139.
12. Cameron, C. E.,, I. M. Moustafa, and, J. J. Arnold. 2009. Dynamics: the missing link between structure and function of the viral RNA-dependent RNA polymerase? Curr. Opin. Struct. Biol. 19: 768774.
13. Campagnola, G.,, M. Weygandt,, K. Scoggin, and, O. Peersen. 2008. Crystal structure of coxsackievirus B3 3D pol highlights the functional importance of residue 5 in picornavirus polymerases. J. Virol. 82: 94589464.
14. Castro, C.,, J. J. Arnold, and, C. E. Cameron. 2005. Incorporation fidelity of the viral RNA-dependent RNA polymerase: a kinetic, thermodynamic and structural perspective. Virus Res. 107: 141149.
15. Charini, W. A.,, C. C. Burns,, E. Ehrenfeld, and, B. L. Semler. 1991. trans rescue of a mutant poliovirus RNA polymerase function. J. Virol. 65: 26552665.
16. Charini, W. A.,, S. Todd,, G. A. Gutman, and, B. L. Semler. 1994. Transduction of a human RNA sequence by poliovirus. J. Virol. 68: 65476552.
17. Cho, M. W.,, O. C. Richards,, T. M. Dmitrieva,, V. Agol, and, E. Ehrenfeld. 1993. RNA duplex unwinding activity of poliovirus RNA-dependent RNA polymerase 3D pol. J. Virol. 67: 30103018.
18. Collis, P. S.,, B. J. O’Donnell,, D. J. Barton,, J. A. Rogers, and, J. B. Flanegan. 1992. Replication of poliovirus RNA and subgenomic RNA transcripts in transfected cells. J. Virol. 66: 64806488.
19. Crawford, N. M., and, D. Baltimore. 1983. Genome-linked protein VPg of poliovirus is present as free VPg and VPg-pUpU in poliovirus-infected cells. Proc. Natl. Acad. Sci. USA 80: 74527455.
20. Crowder, S., and, K. Kirkegaard. 2005. Trans-dominant inhibition of RNA viral replication can slow growth of drug-resistant viruses. Nat. Genet. 37: 701709.
21. Daube, S. S., and, P. H. von Hippel. 1994. RNA displacement pathways during transcription from synthetic RNA-DNA bubble duplexes. Biochemistry 33: 340347.
22. 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: 1992419935.
23. Diamond, S. E., and, K. Kirkegaard. 1994. Clustered charged-to-alanine mutagenesis of poliovirus RNA-dependent RNA polymerase yields multiple temperature-sensitive mutants defective in RNA synthesis. J. Virol. 68: 863876.
24. Dmitrieva, T. M.,, K. B. Norkina, and, V. I. Agol. 1991. Encephalomyocarditis virus RNA polymerase preparations, with and without RNA helicase activity. J. Virol. 65: 27142717.
25. Egger, D., and, K. Bienz. 2002. Recombination of poliovirus RNA proceeds in mixed replication complexes originating from distinct replication start sites. J. Virol. 76: 1096010971.
26. Ferrer-Orta, C.,, A. Arias,, R. Agudo,, R. Perez-Luque,, C. Escarmis,, E. Domingo, and, N. Verdaguer. 2006. The structure of a protein primer-polymerase complex in the initiation of genome replication. EMBO J. 25: 880888.
27. Ferrer-Orta, C.,, A. Arias,, C. Escarmis, and, N. Verdaguer. 2006. A comparison of viral RNA-dependent RNA polymerases. Curr. Opin. Struct. Biol. 16: 2734.
28. Ferrer-Orta, C.,, A. Arias,, R. Perez-Luque,, C. Escarmis,, E. Domingo, and, N. Verdaguer. 2004. Structure of foot-and-mouth disease virus RNA-dependent RNA polymerase and its complex with a template-primer RNA. J. Biol. Chem. 279: 4721247221.
29. Gamarnik, A. V., and, R. Andino. 1998. Switch from translation to RNA replication in a positive-stranded RNA virus. Genes Dev. 12: 22932304.
30. Gamarnik, A. V., and, R. Andino. 1997. Two functional complexes formed by KH domain containing proteins with the 5′ noncoding region of poliovirus RNA. RNA 3: 882892.
31. Giachetti, C.,, S. S. Hwang, and, B. L. Semler. 1992. cis-acting lesions targeted to the hydrophobic domain of a poliovirus membrane protein involved in RNA replication. J. Virol. 66: 60456057.
32. Giaever, G. N.,, L. Snyder, and, J. C. Wang. 1988. DNA super-coiling in vivo. Biophys. Chem. 29: 715.
33. Gruez, A.,, B. Selisko,, M. Roberts,, G. Bricogne,, C. Bussetta,, I. Jabafi,, B. Coutard,, A. M. De Palma,, J. Neyts, and, B. Canard. 2008. The crystal structure of coxsackievirus B3 RNA-dependent RNA polymerase in complex with its protein primer VPg confirms the existence of a second VPg binding site on Picornaviridae polymerases. J. Virol. 82: 95779590.
34. Hall, D. J., and, A. C. Palmenberg. 1996. Cleavage site mutations in the encephalomyocarditis virus P3 region lethally abrogate the normal processing cascade. J. Virol. 70: 59545961.
35. Hansen, J. L.,, A. M. Long, and, S. C. Schultz. 1997. Structure of the RNA-dependent RNA polymerase of poliovirus. Structure 5: 11091122.
36. Harmon, S. A.,, O. C. Richards,, D. F. Summers, and, E. Ehrenfeld. 1991. The 5′-terminal nucleotides of hepatitis A virus RNA, but not poliovirus RNA, are required for infectivity. J. Virol. 65: 27572760.
37. Herold, J., and, R. Andino. 2001. Poliovirus RNA replication requires genome circularization through a protein-protein bridge. Mol. Cell 7: 581591.
38. Hobson, S. D.,, E. S. Rosenblum,, O. C. Richards,, K. Richmond,, K. Kirkegaard, and, S. C. Schultz. 2001. Oligomeric structures of poliovirus polymerase are important for function. EMBO J. 20: 11531163.
39. 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: 94909498.
40. Hsu, N. Y.,, O. Ilnytska,, G. Belov,, M. Santiana,, Y. H. Chen,, P. M. Tavorkian,, C. Pau,, H. Van der Schaar,, N. Kaushik-Basu,, T. Balla,, C. E. Cameron,, E. Ehrenfeld,, F. J. Van Kuppeveld, and, N. Altan-Bonnet. 2010. Viral reorganization of the secretory pathway generates distinct organelles for RNA replication. Cell 141: 799811.
41. Jiang, M.,, N. Ma,, D. G. Vassylyev, and, W. T. McAllister. 2004. RNA displacement and resolution of the transcription bubble during transcription by T7 RNA polymerase. Mol. Cell 15: 777788.
42. Johnson, K. L., and, P. Sarnow. 1991. Three poliovirus 2B mutants exhibit noncomplementable defects in viral RNA amplification and display dosage-dependent dominance over wild-type poliovirus. J. Virol. 65: 43414349.
43. Jurgens, C., and, J. B. Flanegan. 2003. Initiation of poliovirus negative-strand RNA synthesis requires precursor forms of P2 proteins. J. Virol. 77: 10751083.
44. Klump, W. M.,, I. Bergmann,, B. C. Muller,, D. Ameis, and, R. Kandolf. 1990. Complete nucleotide sequence of infectious coxsack-ievirus B3 cDNA: two initial 5′ uridine residues are regained during plus-strand RNA synthesis. J. Virol. 64: 15731583.
45. Kok, C. C., and, P. C. McMinn. 2009. Picornavirus RNA-dependent RNA polymerase. Int. J. Biochem. Cell Biol. 41: 4984502.
46. Kuge, S.,, I. Saito, and, A. Nomoto. 1986. Primary structure of poliovirus defective-interfering particle genomes and possible generation mechanisms of the particles. J. Mol. Biol. 192: 473487.
47. Lawson, M. A., and, B. L. Semler. 1992. Alternate poliovirus nonstructural protein processing cascades generated by primary sites of 3C proteinase cleavage. Virology 191: 309320.
48. Lescar, J., and, B. Canard. 2009. RNA-dependent RNA polymerases from flaviviruses and Picornaviridae. Curr. Opin. Struct. Biol. 19: 759767.
49. Levintow, L., and, J. E. Darnell, Jr. 1960. A simplified procedure for purification of large amounts of poliovirus: characterization and amino acid analysis of type 1 poliovirus. J. Biol. Chem. 235: 7073.
50. Love, R. A.,, K. A. Maegley,, X. Yu,, R. A. Ferre,, L. K. Lingardo,, W. Diehl,, H. E. Parge,, P. S. Dragovich, and, S. A. Fuhrman. 2004. The crystal structure of the RNA-dependent RNA polymerase from human rhinovirus: a dual function target for common cold antiviral therapy. Structure 12: 15331544.
51. Lundquist, R. E., and, J. V. Maizel, Jr. 1978. Structural studies of the RNA component of the poliovirus replication complex. I. Purification and biochemical characterization. Virology 85: 434444.
52. Lyle, J. M.,, E. Bullitt,, K. Bienz, and, K. Kirkegaard. 2002. Visualization and functional analysis of RNA-dependent RNA polymerase lattices. Science 296: 22182222.
53. Lyle, J. M.,, A. Clewell,, K. Richmond,, O. C. Richards,, D. A. Hope,, S. C. Schultz, and, K. Kirkegaard. 2002. Similar structural basis for membrane localization and protein priming by an RNA-dependent RNA polymerase. J. Biol. Chem. 277: 1632416331.
54. Marcotte, L. L.,, A. B. Wass,, D. W. Gohara,, H. B. Pathak,, J. J. Arnold,, D. J. Filman,, C. E. Cameron, and, J. M. Hogle. 2007. Crystal structure of poliovirus 3CD protein: virally encoded protease and precursor to the RNA-dependent RNA polymerase. J. Virol. 81: 35833596.
55. Murray, K. E.,, B. P. Steil,, A. W. Roberts, and, D. J. Barton. 2004. Replication of poliovirus RNA with complete internal ribosome entry site deletions. J. Virol. 78: 13931402.
56. Ng, K. K.,, J. J. Arnold, and, C. E. Cameron. 2008. Structure-function relationships among RNA-dependent RNA polymerases. Curr. Top. Microbiol. Immunol. 320: 137156.
57. Nieva, J. L.,, A. Agirre,, S. Nir, and, L. Carrasco. 2003. Mechanisms of membrane permeabilization by picornavirus 2B viroporin. FEBS Lett. 552: 6873.
58. Novak, J. E., and, K. Kirkegaard. 1994. Coupling between genome translation and replication in an RNA virus. Genes Dev. 8: 17261737.
59. Oh, H. S.,, H. B. Pathak,, I. G. Goodfellow,, J. J. Arnold, and, C. E. Cameron. 2009. Insight into poliovirus genome replication and encapsidation obtained from studies of 3B-3C cleavage site mutants. J. Virol. 83: 93709387.
60. Parsley, T. B.,, J. S. Towner,, L. B. Blyn,, E. Ehrenfeld, and, B. L. Semler. 1997. Poly(rC) binding protein 2 forms a ternary complex with the 5′-terminal sequences of poliovirus RNA and the viral 3CD proteinase. RNA 3: 11241134.
61. Pata, J. D.,, S. C. Schultz, and, K. Kirkegaard. 1995. Functional oligomerization of poliovirus RNA-dependent RNA polymerase. RNA 1: 466477.
62. Patargias, G.,, T. Barke,, A. Watts, and, W. B. Fischer. 2009. Model generation of viral channel forming 2B protein bundles from polio and coxsackie viruses. Mol. Membr. Biol. 26: 309320.
63. Pathak, H. B.,, J. J. Arnold,, P. N. Wiegand,, M. R. Hargittai, and, C. E. Cameron. 2007. Picornavirus genome replication: assembly and organization of the VPg uridylylation ribonucleoprotein (initiation) complex. J. Biol. Chem. 282: 1620216213.
64. Pathak, H. B.,, S. K. Ghosh,, A. W. Roberts,, S. D. Sharma,, J. D. Yoder,, J. J. Arnold,, D. W. Gohara,, D. J. Barton,, A. V. Paul, and, C. E. Cameron. 2002. Structure-function relationships of the RNA-dependent RNA polymerase from poliovirus (3D pol). A surface of the primary oligomerization domain functions in capsid precursor processing and VPg uridylylation. J. Biol. Chem. 277: 3155131562.
65. Paul, A. V.,, J. Mugavero,, A. Molla, and, E. Wimmer. 1998. Internal ribosomal entry site scanning of the poliovirus polyprotein: implications for proteolytic processing. Virology 250: 241253.
66. Paul, A. V.,, J. Mugavero,, J. Yin,, S. Hobson,, S. Schultz,, J. H. van Boom, and, E. Wimmer. 2000. Studies on the attenuation phenotype of polio vaccines: poliovirus RNA polymerase derived from Sabin type 1 sequence is temperature sensitive in the uridylylation of VPg. Virology 272: 7284.
67. Perera, R.,, S. Daijogo,, B. L. Walter,, J. H. Nguyen, and, B. L. Semler. 2007. Cellular protein modification by poliovirus: the two faces of poly(rC)-binding protein. J. Virol. 81: 89198932.
68. Richards, O. C.,, S. C. Martin,, H. G. Jense, and, E. Ehrenfeld. 1984. Structure of poliovirus replicative intermediate RNA. Electron microscope analysis of RNA cross-linked in vivo with psoralen derivative. J. Mol. Biol. 173: 325340.
69. Richards, O. C.,, J. F. Spagnolo,, J. M. Lyle,, S. E. Vleck,, R. D. Kuchta, and, K. Kirkegaard. 2006. Intramolecular and inter-molecular uridylylation by poliovirus RNA-dependent RNA polymerase. J. Virol. 80: 74057415.
70. Roberts, R. W., and, J. W. Szostak. 1997. RNA-peptide fusions for the in vitro selection of peptides and proteins. Proc. Natl. Acad. Sci. USA 94: 1229712302.
71. Schein, C. H.,, N. Oezguen,, D. E. Volk,, R. Garimella,, A. Paul, and, W. Braun. 2006. NMR structure of the viral peptide linked to the genome (VPg) of poliovirus. Peptides 27: 16761684.
72. Shen, M.,, Z. J. Reitman,, Y. Zhao,, I. Moustafa,, Q. Wang,, J. J. Arnold,, H. B. Pathak, and, C. E. Cameron. 2008. Picornavirus genome replication. Identification of the surface of the poliovirus (PV) 3C dimer that interacts with PV 3D pol during VPg uridylylation and construction of a structural model for the PV 3C2-3D pol complex. J. Biol. Chem. 283: 875888.
73. Spagnolo, J. F.,, E. Rossignol,, E. Bullitt, and, K. Kirkegaard. 2010. Enzymatic and nonenzymatic functions of viral RNA-dependent RNA polymerases within oligomeric arrays. RNA 16: 382393.
74. Strauss, D. M.,, L. W. Glustrom, and, D. S. Wuttke. 2003. Towards an understanding of the poliovirus replication complex: the solution structure of the soluble domain of the poliovirus 3A protein. J. Mol. Biol. 330: 225234.
75. Strauss, D. M., and, D. S. Wuttke. 2007. Characterization of protein-protein interactions critical for poliovirus replication: analysis of 3AB and VPg binding to the RNA-dependent RNA polymerase. J. Virol. 81: 63696378.
76. Tellez, A. B.,, S. Crowder,, J. F. Spagnolo,, A. A. Thompson,, O. B. Peersen,, D. L. Brutlag, and, K. Kirkegaard. 2006. Nucleotide channel of RNA-dependent RNA polymerase used for inter-molecular uridylylation of protein primer. J. Mol. Biol. 357: 665675.
77. Thompson, A. A.,, R. A. Albertini, and, O. B. Peersen. 2007. Stabilization of poliovirus polymerase by NTP binding and fingers-thumb interactions. J. Mol. Biol. 366: 14591474.
78. Thompson, A. A., and, O. B. Peersen. 2004. Structural basis for proteolysis-dependent activation of the poliovirus RNA-dependent RNA polymerase. EMBO J. 23: 34623471.
79. Tiley, L.,, A. M. King, and, G. J. Belsham. 2003. The foot-and-mouth disease virus cis-acting replication element (cre) can be complemented in trans within infected cells. J. Virol. 77: 22432246.
80. Towner, J. S.,, M. M. Mazanet, and, B. L. Semler. 1998. Rescue of defective poliovirus RNA replication by 3AB-containing precursor polyproteins. J. Virol. 72: 71917200.
81. Wang, J. C. 2002. Cellular roles of DNA topoisomerases: a molecular perspective. Nat. Rev. Mol. Cell Biol. 3: 430440.
82. Xiang, W.,, A. Cuconati,, D. Hope,, K. Kirkegaard, and, E. Wimmer. 1998. Complete protein linkage map of poliovirus P3 proteins: interaction of polymerase 3D pol with VPg and with genetic variants of 3AB. J. Virol. 72: 67326741.
83. Xiang, W.,, A. Cuconati,, A. V. Paul,, X. Cao, and, E. Wimmer. 1995. Molecular dissection of the multifunctional poliovirus RNA-binding protein 3AB. RNA 1: 892904.
84. Zhang, X.,, S. B. Walker,, P. R. Chipman,, M. L. Nibert, and, T. S. Baker. 2003. Reovirus polymerase lambda 3 localized by cryo-electron microscopy of virions at a resolution of 7.6 Å. Nat. Struct. Biol. 10: 10111018.
85. Zimmerman, E. F.,, M. Heeter, and, J. E. Darnell. 1963. RNA synthesis in poliovirus-infected cells. Virology 19: 400408.


Generic image for table
Table 1.

Effects of various postulated polymerase-polymerase, polymerase-3C, and 3C-3C contacts on viral viability

Citation: Kirkegaard K, Semler B. 2010. Genome Replication II: the Process, p 127-140. In Ehrenfeld E, Domingo E, Roos R (ed), The Picornaviruses. ASM Press, Washington, DC. doi: 10.1128/9781555816698.ch8

This is a required field
Please enter a valid email address
Please check the format of the address you have entered.
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error