Source: http://www.asmscience.org/content/book/10.1128/9781555816698.ch09
Timestamp: 2019-04-24 18:54:23+00:00

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This chapter addresses the main features concerning picornavirus gene expression. Picornavirus genomes are tightly packed; the RNA encodes a single poly protein whose translation is governed by the internal ribosome entry site (IRES) element using a cap-independent mechanism that hijacks the translation machinery. Picornavirus IRES activity depends on the coordination of RNA structure and RNA-protein interactions. RNA probing of the entire element revealed long-distance interactions within the 5&apos; untranslated region (UTR) of coxsackievirus B3 (CVB3), thereby providing information on overall IRES structure. Despite the fact that many IRES trans-acting factors (ITAFs) are promiscuous RNA-binding proteins, IRESs exhibit distinct requirements in terms of functional RNA-protein associations. Ribonucleoprotein complexes assembled on IRESs share various components with the spliceosome, as in the case of SRp20, polypyrimidine tract-binding protein (PTB), or hnRNP A1. Most of the knowledge on factors required for IRES activity comes from in vitro assays. The study of IRES-ribonucleoprotein complexes in living cells has been addressed using reagents that are permeable to the cell membrane and recognize RNA molecules in a structure-dependent manner. Picornaviral genome RNAs encode their proteins in a single, long open reading frame (ORF), translated into a single poly protein. The presence of 3C and 3C-like proteinase domains in a wide range of positive-stranded RNA virus poly proteins argues strongly that this proteolytic domain was acquired at an early stage in the evolution of these viruses.
Primary polyprotein cleavages. (A) The polyprotein organization (boxed areas) is shown for viruses in which the primary polyprotein cleavage between the capsid proteins and replication protein precursors have been shown, or are assumed, to be mediated by the 3C proteinase (3Cpro). Primary cleavages are shown as curved arrows, and regions involved in processing are shown by darker shading. (B) Polyproteins in which the primary cleavage between the capsid proteins and replication protein precursors is mediated by the 2A translational recoding sequence (CHYSEL). All polyproteins here encode an L protein, but only in the case of the aphtho- and erboviruses is L a proteinase (Lpro), which mediates a primary cleavage at its own C terminus. (C) The enteroviruses have been shown to possess a proteolytic form of 2A protein (2Apro), and the sapeloviruses SV2 and PEV8 are also thought to possess this form of 2A. In all cases a primary cleavage, mediated by 3Cpro, occurs at the 2C/3A site. Designations for the different primary cleavage products generated are shown inside brackets.
Secondary polyprotein processing. Secondary processing events mediated by 3Cpro are shown as curved arrows. (A) Enterovirus capsid protein precursors (P1) are processed by the 3CD proteinase (3CDpro) rather than 3Cpro. The 3D polymerase may be cleaved by 2Apro to produce 3C′ and 3D′ (vertical arrow). The 1A/1B (VP4/VP2) maturation cleavage occurs concomitantly with the encapsidation of vRNA by an unknown mechanism. (B) In aphthoviruses the capsid protein precursor (P1-2A) may be processed by 3Cpro, but it is processed more efficiently by 3DCpro. The 2A oligopeptide (18 aa) is trimmed away from 1D by 3Cpro or 3CDpro. Secondary processing of the P3 precursor is highly complex, as the multiple 3B (VPg) proteins give rise to a series of alternative processing events generating the 3AB and 3CD complex of protein bands seen on SDS-PAGE gels. (C) In viruses with the nonproteolytic forms of L and 2A proteins (typified here by cardioviruses), these proteins are processed by 3Cpro or 3CDpro. The host cell proteinase cleavage of the hepatovirus 1D/2A site is represented by a dotted, vertical arrow.
Proteinase active site residues and the 2A CHYSEL motif. Residues comprising the catalytic triad of the 3C, 2A, and L proteinases are shown (bold, shaded, and with an asterisk, respectively) for representative sequences. For 3Cpro: rhinovirus (HRV2), enterovirus (PV-1), sapelovirus (SV2), hepatovirus (HAV), tremovirus (avian encephalomyelitis virus), aphthovirus (FMDV), cardiovirus (EMCV), senecavirus (Seneca Valley virus), teschovirus (porcine teschovirus 1), cosavirus (human cosa-virus A1), erbovirus (ERBV1), kobuvirus (BK virus), and parechovirus (ECHO-22). For 2Apro: rhinovirus (HRV2), enterovirus (PV-1), and sapelovirus (SV2). For Lpro: aphthoviruses FMDV, equine rhinitis A virus (ERAV), and bovine rhinitis B virus (BRBV) and the erbovirus equine rhinitis B virus 1. The alignments shown are taken from alignments of all available sequences, together with residues that are completely conserved (bold and shaded) or highly conserved (shaded) among all sequences. Unaligned 2A CHYSEL sequences are shown for aphthovirus (FMDV), erbovirus (ERBV1), teschovirus (PTV-1), cardioviruses (EMCV, TMEV, and Saffold virus), seal picornavirus, human cosavirus A1, Ljungan virus, and duck hepatitis A virus (avihepatovirus). Along with the conserved residues in the C-terminal motif (bold and shaded), 3Cpro cleavage sites (bold) by which the oligopeptide forms of 2A are trimmed from 1D are shown.
Sequence diversity of 3C and 2A proteinases. All 2Apro and 3Cpro sequences were aligned using ClustalX. The phylo-gram was constructed using Dendroscope, and representative members of branches were chosen to illustrate the extent of sequence diversity. 3Cpro sequences are considerably more diverse than those of 2Apro. Although the sapelovirus 2As appear to be slightly more related to 3Cpro, examination of the alignments shows that relative to 2Apro, sapelovirus 2A bears three large insertions within the N-terminal region but has high similarity with the C-terminal domain of 2Apro.
Scheme of 2A CHYSEL translational recoding. Peptidyl-tRNA is located in the ribosome A-site (step a). Peptidyl-tRNA is translocated to the P-site, allowing ingress of prolyl-tRNA into the A-site (step b). Interaction of 2A with the ribosome exit tunnel, plus the tight turn, precludes the peptidyl-tRNA ester linkage from nucleophilic attack, as prolyl-tRNA dissociates from the ribosome (step c). eRF1 enters the A-site (step d) and hydrolyzes the ester bond (step e). eRF1 leaves the A-site (promoted by eRF3), and the nascent peptide is released from the ribosome (step f). Prolyl-tRNA (re)enters the A-site (step g) and is translocated to the P-site by eEF2 (step h). The next amino-acyl-tRNA enters the A-site, and sequences downstream of 2A are translated (step i). An alternative outcome is that the ribosome subunits may dissociate and translation is terminated. Our model predicts this could occur at any of the stages indicated in steps f to i.
1. Allaire, M.,, M. M. Chernaia,, B. A. Malcolm, and, M. N. James. 1994. Picornaviral 3C cysteine proteinases have a fold similar to chymotrypsin-like serine proteinases. Nature 369: 72– 76.
2. Amineva, S. P.,, A. G. Aminev,, A. C. Palmenberg, and, J. E. Gern. 2004. Rhinovirus 3C protease precursors 3CD and 3CD′ localize to the nuclei of infected cells. J. Gen. Virol. 85: 2969– 2979.
3. 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: 3587– 3598.
4. Andino, R.,, G. E. Rieckhof, and, D. Baltimore. 1990. A functional ribonucleoprotein complex forms around the 5′ end of poliovirus RNA. Cell 63: 369– 380.
5. Andino, R.,, G. E. Rieckhof,, D. Trono, and, D. Baltimore. 1990. Substitutions in the protease (3C pro) gene of poliovirus can suppress a mutation in the 5′ noncoding region. J. Virol. 64: 607– 612.
6. Andreev, D. E.,, O. Fernandez-Miragall,, J. Ramajo,, S. E. Dmitriev,, I. M. Terenin,, E. Martinez-Salas, and, I. N. Shatsky. 2007. Differential factor requirement to assemble translation initiation complexes at the alternative start codons of foot-and-mouth disease virus RNA. RNA 13: 1366– 1374.
7. Argos, P.,, G. Kamer,, M. J. Nicklin, and, E. Wimmer. 1984. Similarity in gene organization and homology between proteins of animal picornaviruses and a plant comovirus suggest common ancestry of these virus families. Nucleic Acids Res. 12: 7251– 7267.
8. Atkins, J. F.,, N. M. Wills,, G. Loughran,, C. Y. Wu,, K. Parsawar,, M. D. Ryan,, C. H. Wang, and, C. C. Nelson. 2007. A case for “StopGo”: reprogramming translation to augment codon meaning of GGN by promoting unconventional termination (Stop) after addition of glycine and then allowing continued translation (Go). RNA 13: 803– 810.
9. Bailey, J. M., and, W. E. Tapprich. 2007. Structure of the 5′ nontranslated region of the coxsackievirus B3 genome: chemical modification and comparative sequence analysis. J. Virol. 81: 650– 668.
10. Bakhshesh, M.,, E. Groppelli,, M. M. Willcocks,, E. Royall,, G. J. Belsham, and, L. O. Roberts. 2008. The picornavirus avian encephalomyelitis virus possesses a hepatitis C virus-like internal ribosome entry site element. J. Virol. 82: 1993– 2003.
11. Batson, S., and, K. Rundell. 1991. Proteolysis at the 2A/2B junction in Theiler’s murine encephalomyelitis virus. Virology 181: 764– 767.
12. Battle, D. J.,, C. K. Lau,, L. Wan,, H. Deng,, F. Lotti, and, G. Dreyfuss. 2006. The Gemin5 protein of the SMN complex identifies snRNAs. Mol. Cell 23: 273– 279.
13. Baum, E. Z.,, G. A. Bebernitz,, O. Palant,, T. Mueller, and, S. J. Plotch. 1991. Purification, properties, and mutagenesis of poliovirus 3C protease. Virology 185: 140– 150.
14. Baxter, N. J.,, A. Roetzer,, H. D. Liebig,, S. E. Sedelnikova,, A. M. Hounslow,, T. Skern, and, J. P. Waltho. 2006. Structure and dynamics of coxsackievirus B4 2A proteinase, an enyzme involved in the etiology of heart disease. J. Virol. 80: 1451– 1462.
15. Bazan, J. F., and, R. J. Fletterick. 1988. Viral cysteine proteases are homologous to the trypsin-like family of serine proteases: structural and functional implications. Proc. Natl. Acad. Sci. USA 85: 7872– 7876.
16. Bedard, K. M.,, S. Daijogo, and, B. L. Semler. 2007. A nucleocytoplasmic SR protein functions in viral IRES-mediated translation initiation. EMBO J. 26: 459– 467.
17. Belsham, G. J. 2009. Divergent picornavirus IRES elements. Virus Res. 139: 183– 192.
18. Belsham, G. J. 1992. Dual initiation sites of protein synthesis on foot-and-mouth disease virus RNA are selected following internal entry and scanning of ribosomes in vivo. EMBO J. 11: 1105– 1110.
19. Bergmann, E. M.,, S. C. Mosimann,, M. M. Chernaia,, B. A. Malcolm, and, M. N. James. 1997. The refined crystal structure of the 3C gene product from hepatitis A virus: specific proteinase activity and RNA recognition. J. Virol. 71: 2436– 2448.
20. Birtley, J. R., and, S. Curry. 2005. Crystallization of foot-and-mouth disease virus 3C protease: surface mutagenesis and a novel crystal-optimization strategy. Acta Crystallogr. D 61: 646– 650.
21. Bjorndahl, T. C.,, L. C. Andrew,, V. Semenchenko, and, D. S. Wishart. 2007. NMR solution structures of the apo and peptide-inhibited human rhinovirus 3C protease (serotype 14): structural and dynamic comparison. Biochemistry 46: 12945– 12958.
22. Black, W. D.,, C. A. Hartley,, N. P. Ficorilli, and, M. J. Studdert. 2009. Virion associated proteins of equine rhinitis B virus 1 (ERBV1): the non-structural protein 3C pro co-purifies with virions. Virus Res. 140: 205– 208.
23. Blair, W. S.,, J. H. Nguyen,, T. B. Parsley, and, B. L. Semler. 1996. Mutations in the poliovirus 3CD proteinase S1-specificity pocket affect substrate recognition and RNA binding. Virology 218: 1– 13.
24. Blyn, L. B.,, J. S. Towner,, B. L. Semler, and, E. Ehrenfeld. 1997. Requirement of poly(rC) binding protein 2 for translation of poliovirus RNA. J. Virol. 71: 6243– 6246.
25. Burroughs, J. N.,, D. V. Sangar,, B. E. Clarke,, D. J. Rowlands,, A. Billiau, and, D. Collen. 1984. Multiple proteases in foot-and-mouth disease virus replication. J. Virol. 50: 878– 883.
26. Cao, X.,, I. E. Bergmann,, R. Fullkrug, and, E. Beck. 1995. Functional analysis of the two alternative translation initiation sites of foot-and-mouth disease virus. J. Virol. 69: 560– 563.
27. Chard, L. S.,, Y. Kaku,, B. Jones,, A. Nayak, and, G. J. Belsham. 2006. Functional analyses of RNA structures shared between the internal ribosome entry sites of hepatitis C virus and the picornavirus porcine teschovirus 1 Talfan. J. Virol. 80: 1271– 1279.
28. Cheah, K. C.,, L. E. Leong, and, A. G. Porter. 1990. Site-directed mutagenesis suggests close functional relationship between a human rhinovirus 3C cysteine protease and cellular trypsin-like serine proteases. J. Biol. Chem. 265: 7180– 7187.
29. Chen, C. Y., and, P. Sarnow. 1995. Initiation of protein synthesis by the eukaryotic translational apparatus on circular RNAs. Science 268: 415– 417.
30. Clarke, B. E., and, D. V. Sangar. 1988. Processing and assembly of foot-and-mouth disease virus proteins using subgenomic RNA. J. Gen. Virol. 69: 2313– 2325.
31. Clarke, B. E.,, D. V. Sangar,, J. N. Burroughs,, S. E. Newton,, A. R. Carroll, and, D. J. Rowlands. 1985. Two initiation sites for foot-and-mouth disease virus polyprotein in vivo. J. Gen. Virol. 66: 2615– 2626.
32. Cohen, L.,, D. Benichou, and, A. Martin. 2002. Analysis of deletion mutants indicates that the 2A polypeptide of hepatitis A virus participates in virion morphogenesis. J. Virol. 76: 7495– 7505.
33. Conte, M. R.,, T. Grune,, J. Ghuman,, G. Kelly,, A. Ladas,, S. Matthews, and, S. Curry. 2000. Structure of tandem RNA recognition motifs from polypyrimidine tract binding protein reveals novel features of the RRM fold. EMBO J. 19: 3132– 3141.
34. Cornell, C. T., and, B. L. Semler. 2002. Subdomain specific functions of the RNA polymerase region of poliovirus 3CD polypeptide. Virology 298: 200– 213.
35. Curry, S.,, N. Roque-Rosell,, T. R. Sweeney,, P. A. Zunszain, and, R. J. Leatherbarrow. 2007. Structural analysis of foot-and-mouth disease virus 3C protease: a viable target for antiviral drugs? Biochem. Soc. Trans. 35: 594– 598.
36. de Breyne, S.,, Y. Yu,, A. Unbehaun,, T. V. Pestova, and, C. U. Hellen. 2009. Direct functional interaction of initiation factor eIF4G with type 1 internal ribosomal entry sites. Proc. Natl. Acad. Sci. USA 106: 9197– 9202.
37. de Felipe, P.,, L. E. Hughes,, M. D. Ryan, and, J. D. Brown. 2003. Co-translational, intraribosomal cleavage of polypeptides by the foot-and-mouth disease virus 2A peptide. J. Biol. Chem. 278: 11441– 11448.
38. Dewalt, P. G.,, M. A. Lawson,, R. J. Colonno, and, B. L. Semler. 1989. Chimeric picornavirus polyproteins demonstrate a common 3C proteinase substrate specificity. J. Virol. 63: 3444– 3452.
39. Dobrikova, E.,, P. Florez,, S. Bradrick, and, M. Gromeier. 2003. Activity of a type 1 picornavirus internal ribosomal entry site is determined by sequences within the 3′ nontranslated region. Proc. Natl. Acad. Sci. USA 100: 15125– 15130.
40. Donnelly, M. L.,, D. Gani,, M. Flint,, S. Monaghan, and, M. D. Ryan. 1997. The cleavage activities of aphthovirus and cardio-virus 2A proteins. J. Gen. Virol. 78: 13– 21.
41. Donnelly, M. L.,, G. Luke,, A. Mehrotra,, X. Li,, L. E. Hughes,, D. Gani, and, M. D. Ryan. 2001. Analysis of the aphthovirus 2A/2B polyprotein ‘cleavage’ mechanism indicates not a proteolytic reaction, but a novel translational effect: a putative ribosomal ‘skip.’ J. Gen. Virol. 82: 1013– 1025.
42. Doronina, V. A.,, C. Wu,, P. de Felipe,, M. S. Sachs,, M. D. Ryan, and, J. D. Brown. 2008. Site-specific release of nascent chains from ribosomes at a sense codon. Mol. Cell. Biol. 28: 4227– 4239.
43. Du, Z.,, N. B. Ulyanov,, J. Yu,, R. Andino, and, T. L. James. 2004. NMR structures of loop B RNAs from the stem-loop IV domain of the enterovirus internal ribosome entry site: a single C to U substitution drastically changes the shape and flexibility of RNA. Biochemistry 43: 5757– 5771.
44. Evans, D. M.,, G. Dunn,, P. D. Minor,, G. C. Schild,, A. J. Cann,, G. Stanway,, J. W. Almond,, K. Currey, and, J. V. Maizel, Jr. 1985. Increased neurovirulence associated with a single nucleotide change in a noncoding region of the Sabin type 3 poliovaccine genome. Nature 314: 548– 550.
45. Farazi, T. A.,, G. Waksman, and, J. I. Gordon. 2001. The biology and enzymology of protein N-myristoylation. J. Biol. Chem. 276: 39501– 39504.
46. Fernandez-Miragall, O.,, S. Lopez de Quinto, and, E. Martinez-Salas. 2009. Relevance of RNA structure for the activity of picornavirus IRES elements. Virus Res. 139: 172– 182.
47. Fernandez-Miragall, O., and, E. Martinez-Salas. 2007. In vivo footprint of a picornavirus internal ribosome entry site reveals differences in accessibility to specific RNA structural elements. J. Gen. Virol. 88: 3053– 3062.
48. Fernandez-Miragall, O., and, E. Martinez-Salas. 2003. Structural organization of a viral IRES depends on the integrity of the GNRA motif. RNA 9: 1333– 1344.
49. Fernandez-Miragall, O.,, R. Ramos,, J. Ramajo, and, E. Martinez-Salas. 2006. Evidence of reciprocal tertiary interactions between conserved motifs involved in organizing RNA structure essential for internal initiation of translation. RNA 12: 223– 234.
50. Flint, M. 1995. A study of foot-and-mouth disease virus polyprotein processing. Thesis. University of Reading, Reading, United Kingdom.
51. Florez, P. M.,, O. M. Sessions,, E. J. Wagner,, M. Gromeier, and, M. A. Garcia-Blanco. 2005. The polypyrimidine tract binding protein is required for efficient picornavirus gene expression and propagation. J. Virol. 79: 6172– 6179.
52. Gamarnik, A. V.,, N. Boddeker, and, R. Andino. 2000. Translation and replication of human rhinovirus type 14 and mengo-virus in Xenopus oocytes. J. Virol. 74: 11983– 11987.
53. Gorbalenya, A. E.,, V. M. Blinov, and, A. P. Donchenko. 1986. Poliovirus-encoded proteinase 3C: a possible evolutionary link between cellular serine and cysteine proteinase families. FEBS Lett. 194: 253– 257.
54. Gorbalenya, A. E.,, A. P. Donchenko,, V. M. Blinov, and, E. V. Koonin. 1989. Cysteine proteases of positive strand RNA viruses and chymotrypsin-like serine proteases. A distinct protein superfamily with a common structural fold. FEBS Lett. 243: 103– 114.
55. Gorbalenya, A. E.,, E. V. Koonin, and, M. M. Lai. 1991. Putative papain-related thiol proteases of positive-strand RNA viruses. Identification of rubi- and aphthovirus proteases and delineation of a novel conserved domain associated with proteases of rubi-, alpha- and coronaviruses. FEBS Lett. 288: 201– 205.
56. Gorbalenya, A. E.,, Y. V. Svitkin,, Y. A. Kazachkov, and, V. I. Agol. 1979. Encephalomyocarditis virus-specific polypeptide p22 is involved in the processing of the viral precursor polypeptides. FEBS Lett. 108: 1– 5.
57. Gosert, R.,, K. H. Chang,, R. Rijnbrand,, M. Yi,, D. V. Sangar, and, S. M. Lemon. 2000. Transient expression of cellular polypyrimidine-tract binding protein stimulates cap-independent translation directed by both picornaviral and flaviviral internal ribosome entry sites in vivo. Mol. Cell. Biol. 20: 1583– 1595.
58. Graff, J.,, O. C. Richards,, K. M. Swiderek,, M. T. Davis,, F. Rusnak,, S. A. Harmon,, X. Y. Jia,, D. F. Summers, and, E. Ehrenfeld. 1999. Hepatitis A virus capsid protein VP1 has a heterogeneous C terminus. J. Virol. 73: 6015– 6023.
59. Grubman, M. J.,, M. Zellner,, G. Bablanian,, P. W. Mason, and, M. E. Piccone. 1995. Identification of the active-site residues of the 3C proteinase of foot-and-mouth disease virus. Virology 213: 581– 589.
60. Guarne, A.,, J. Tormo,, R. Kirchweger,, D. Pfistermueller,, I. Fita, and, T. Skern. 1998. Structure of the foot-and-mouth disease virus leader protease: a papain-like fold adapted for self-processing and eIF4G recognition. EMBO J. 17: 7469– 7479.
61. Guerrier-Takada, C.,, A. van Belkum,, C. W. Pleij, and, S. Altman. 1988. Novel reactions of RNAase P with a tRNA-like structure in turnip yellow mosaic virus RNA. Cell 53: 267– 272.
62. Hammerle, T.,, C. U. Hellen, and, E. Wimmer. 1991. Site-directed mutagenesis of the putative catalytic triad of poliovirus 3C proteinase. J. Biol. Chem. 266: 5412– 5416.
63. Hanecak, R.,, B. L. Semler,, C. W. Anderson, and, E. Wimmer. 1982. Proteolytic processing of poliovirus polypeptides: antibodies to polypeptide P3-7c inhibit cleavage at glutamine-glycine pairs. Proc. Natl. Acad. Sci. USA 79: 3973– 3977.
64. Harmon, S. A.,, W. Updike,, X. Y. Jia,, D. F. Summers, and, E. Ehrenfeld. 1992. Polyprotein processing in cis and in trans by hepatitis A virus 3C protease cloned and expressed in Escherichia coli. J. Virol. 66: 5242– 5247.
65. Harris, K. S.,, W. Xiang,, L. Alexander,, W. S. Lane,, A. V. Paul, and, E. Wimmer. 1994. Interaction of poliovirus polypeptide 3CDpro with the 5′ and 3′ termini of the poliovirus genome. Identification of viral and cellular cofactors needed for efficient binding. J. Biol. Chem. 269: 27004– 27014.
66. Hellen, C. U., and, S. de Breyne. 2007. A distinct group of hepacivirus/pestivirus-like internal ribosomal entry sites in members of diverse picornavirus genera: evidence for modular exchange of functional noncoding RNA elements by recombination. J. Virol. 81: 5850– 5863.
67. Hellen, C. U.,, M. Facke,, H. G. Krausslich,, C. K. Lee, and, E. Wimmer. 1991. Characterization of poliovirus 2A proteinase by mutational analysis: residues required for autocatalytic activity are essential for induction of cleavage of eukaryotic initiation factor 4F polypeptide p220. J. Virol. 65: 4226– 4231.
68. Hellen, C. U.,, C. K. Lee, and, E. Wimmer. 1992. Determinants of substrate recognition by poliovirus 2A proteinase. J. Virol. 66: 3330– 3338.
69. Heras, S. R.,, M. C. Thomas,, M. Garcia-Canadas,, P. de Felipe,, J. L. Garcia-Perez,, M. D. Ryan, and, M. C. Lopez. 2006. L1Tc non-LTR retrotransposons from Trypanosoma cruzi contain a functional viral-like self-cleaving 2A sequence in frame with the active proteins they encode. Cell. Mol. Life Sci. 63: 1449– 1460.
70. Hollister, J. R.,, A. Vagnozzi,, N. J. Knowles, and, E. Rieder. 2008. Molecular and phylogenetic analyses of bovine rhinovirus type 2 shows it is closely related to foot-and-mouth disease virus. Virology 373: 411– 425.
71. Hunt, S. L.,, J. J. Hsuan,, N. Totty, and, R. J. Jackson. 1999. unr, a cellular cytoplasmic RNA-binding protein with five cold-shock domains, is required for internal initiation of translation of human rhinovirus RNA. Genes Dev. 13: 437– 448.
72. Jackson, R. J. 1986. A detailed kinetic analysis of the in vitro synthesis and processing of encephalomyocarditis virus products. Virology 149: 114– 127.
73. Jang, S. K.,, H. G. Krausslich,, M. J. Nicklin,, G. M. Duke,, A. C. Palmenberg, and, E. Wimmer. 1988. A segment of the 5′ non-translated region of encephalomyocarditis virus RNA directs internal entry of ribosomes during in vitro translation. J. Virol. 62: 2636– 2643.
74. Jang, S. K., and, E. Wimmer. 1990. Cap-independent translation of encephalomyocarditis virus RNA: structural elements of the internal ribosomal entry site and involvement of a cellular 57-kD RNA-binding protein. Genes Dev. 4: 1560– 1572.
75. Jia, X. Y.,, E. Ehrenfeld, and, D. F. Summers. 1991. Proteolytic activity of hepatitis A virus 3C protein. J. Virol. 65: 2595– 2600.
76. Jia, X. Y.,, D. F. Summers, and, E. Ehrenfeld. 1993. Primary cleavage of the HAV capsid protein precursor in the middle of the proposed 2A coding region. Virology 193: 515– 519.
77. Jore, J.,, B. De Geus,, R. J. Jackson,, P. H. Pouwels, and, B. E. Enger-Valk. 1988. Poliovirus protein 3CD is the active protease for processing of the precursor protein P1 in vitro. J. Gen. Virol. 69: 1627– 1636.
78. Kafasla, P.,, N. Morgner,, T. A. Poyry,, S. Curry,, C. V. Robinson, and, R. J. Jackson. 2009. Polypyrimidine tract binding protein stabilizes the encephalomyocarditis virus IRES structure via binding multiple sites in a unique orientation. Mol. Cell 34: 556– 568.
79. Kaminski, A.,, G. J. Belsham, and, R. J. Jackson. 1994. Translation of encephalomyocarditis virus RNA: parameters influencing the selection of the internal initiation site. EMBO J. 13: 1673– 1681.
80. Kean, K. M.,, M. T. Howell,, S. Grunert,, M. Girard, and, R. J. Jackson. 1993. Substitution mutations at the putative catalytic triad of the poliovirus 3C protease have differential effects on cleavage at different sites. Virology 194: 360– 364.
81. Kean, K. M.,, N. L. Teterina,, D. Marc, and, M. Girard. 1991. Analysis of putative active site residues of the poliovirus 3C protease. Virology 181: 609– 619.
83. Kolupaeva, V. G.,, I. B. Lomakin,, T. V. Pestova, and, C. U. Hellen. 2003. Eukaryotic initiation factors 4G and 4A mediate conformational changes downstream of the initiation codon of the encephalomyocarditis virus internal ribosomal entry site. Mol. Cell. Biol. 23: 687– 698.
84. Kolupaeva, V. G.,, T. V. Pestova,, C. U. Hellen, and, I. N. Shatsky. 1998. Translation eukaryotic initiation factor 4G recognizes a specific structural element within the internal ribosome entry site of encephalomyocarditis virus RNA. J. Biol. Chem. 273: 18599– 18604.
85. Konig, H., and, B. Rosenwirth. 1988. Purification and partial characterization of poliovirus protease 2A by means of a functional assay. J. Virol. 62: 1243– 1250.
86. Korant, B.,, N. Chow,, M. Lively, and, J. Powers. 1979. Virus-specified protease in poliovirus-infected HeLa cells. Proc. Natl. Acad. Sci. USA 76: 2992– 2995.
87. Korant, B. D.,, J. Brzin, and, V. Turk. 1985. Cystatin, a protein inhibitor of cysteine proteases alters viral protein cleavages in infected human cells. Biochem. Biophys. Res. Commun. 127: 1072– 1076.
88. 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.
89. Lawrence, C., and, R. E. Thach. 1975. Identification of a viral protein involved in posttranslational maturation of the encephalomyocarditis virus capsid precursor. J. Virol. 15: 918– 928.
90. 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.
91. Lawson, M. A., and, B. L. Semler. 1990. Picornavirus protein processing: enzymes, substrates, and genetic regulation. Curr. Top. Microbiol. Immunol. 161: 49– 87.
92. Lee, C. K., and, E. Wimmer. 1988. Proteolytic processing of poliovirus polyprotein: elimination of 2A pro-mediated, alternative cleavage of polypeptide 3CD by in vitro mutagenesis. Virology 166: 405– 414.
93. Leong, L. E.,, P. A. Walker, and, A. G. Porter. 1993. Human rhinovirus-14 protease 3C (3C pro) binds specifically to the 5′-noncoding region of the viral RNA. Evidence that 3C pro has different domains for the RNA binding and proteolytic activities. J. Biol. Chem. 268: 25735– 25739.
94. Le Roy, F.,, T. Salehzada,, C. Bisbal,, J. P. Dougherty, and, S. W. Peltz. 2005. A newly discovered function for RNase L in regulating translation termination. Nat. Struct. Mol. Biol. 12: 505– 512.
95. Li, X. L.,, J. A. Blackford, and, B. A. Hassel. 1998. RNase L mediates the antiviral effect of interferon through a selective reduction in viral RNA during encephalomyocarditis virus infection. J. Virol. 72: 2752– 2759.
96. Lin, J. Y.,, S. R. Shih,, M. Pan,, C. Li,, C. F. Lue,, V. Stollar, and, M. L. Li. 2009. hnRNP A1 interacts with the 5′ untranslated regions of enterovirus 71 and Sindbis virus RNA and is required for viral replication. J. Virol. 83: 6106– 6114.
97. Liu, Z.,, C. M. Carthy,, P. Cheung,, L. Bohunek,, J. E. Wilson,, B. M. McManus, and, D. Yang. 1999. Structural and functional analysis of the 5′ untranslated region of coxsackievirus B3 RNA: in vivo translational and infectivity studies of full-length mutants. Virology 265: 206– 217.
98. Lopez de Quinto, S.,, E. Lafuente, and, E. Martinez-Salas. 2001. IRES interaction with translation initiation factors: functional characterization of novel RNA contacts with eIF3, eIF4B, and eIF4GII. RNA 7: 1213– 1226.
99. Lopez de Quinto, S., and, E. Martinez-Salas. 1997. Conserved structural motifs located in distal loops of aphthovirus internal ribosome entry site domain 3 are required for internal initiation of translation. J. Virol. 71: 4171– 4175.
100. Lopez de Quinto, S., and, E. Martinez-Salas. 2000. Interaction of the eIF4G initiation factor with the aphthovirus IRES is essential for internal translation initiation in vivo. RNA 6: 1380– 1392.
101. Lopez de Quinto, S., and, E. Martinez-Salas. 1999. Involvement of the aphthovirus RNA region located between the two functional AUGs in start codon selection. Virology 255: 324– 336.
102. Lopez de Quinto, S.,, M. Saiz,, D. de la Morena,, F. Sobrino, and, E. Martinez-Salas. 2002. IRES-driven translation is stimulated separately by the FMDV 3′-NCR and poly(A) sequences. Nucleic Acids Res. 30: 4398– 4405.
103. Luke, G. A.,, P. de Felipe,, A. Lukashev,, S. E. Kallioinen,, E. A. Bruno, and, M. D. Ryan. 2008. Occurrence, function and evolutionary origins of ‘2A-like’ sequences in virus genomes. J. Gen. Virol. 89: 1036– 1042.
104. Luz, N., and, E. Beck. 1991. Interaction of a cellular 57-kilodalton protein with the internal translation initiation site of foot-and-mouth disease virus. J. Virol. 65: 6486– 6494.
105. Malnou, C. E.,, T. A. Poyry,, R. J. Jackson, and, K. M. Kean. 2002. Poliovirus internal ribosome entry segment structure alterations that specifically affect function in neuronal cells: molecular genetic analysis. J. Virol. 76: 10617– 10626.
106. 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: 3583– 3596.
107. Marie, I.,, D. Rebouillat, and, A. G. Hovanessian. 1999. The expression of both domains of the 69/71 kDa 2′, 5′ oligoadenylate synthetase generates a catalytically active enzyme and mediates an anti-viral response. Eur. J. Biochem. 262: 155– 165.
108. Martin, A.,, D. Benichou,, S. F. Chao,, L. M. Cohen, and, S. M. Lemon. 1999. Maturation of the hepatitis A virus capsid protein VP1 is not dependent on processing by the 3C pro proteinase. J. Virol. 73: 6220– 6227.
109. Martinez-Salas, E. 2008. The impact of RNA structure on picornavirus IRES activity. Trends Microbiol. 16: 230– 237.
110. Martinez-Salas, E. 1999. Internal ribosome entry site biology and its use in expression vectors. Curr. Opin. Biotechnol. 10: 458– 464.
111. Martinez-Salas, E., and, O. Fernandez-Miragall. 2004. Picornavirus IRES: structure function relationship. Curr. Pharm. Des. 10: 3757– 3767.
112. Martinez-Salas, E.,, S. Lopez de Quinto,, R. Ramos, and, O. Fernandez-Miragall. 2002. IRES elements: features of the RNA structure contributing to their activity. Biochimie 84: 755– 763.
113. Martinez-Salas, E.,, A. Pacheco,, P. Serrano, and, N. Fernandez. 2008. New insights into internal ribosome entry site elements relevant for viral gene expression. J. Gen. Virol. 89: 611– 626.
114. Martinez-Salas, E.,, R. Ramos,, E. Lafuente, and, S. Lopez de Quinto. 2001. Functional interactions in internal translation initiation directed by viral and cellular IRES elements. J. Gen. Virol. 82: 973– 984.
115. Martinez-Salas, E.,, M. P. Regalado, and, E. Domingo. 1996. Identification of an essential region for internal initiation of translation in the aphthovirus internal ribosome entry site and implications for viral evolution. J. Virol. 70: 992– 998.
116. Martinez-Salas, E.,, J. C. Saiz,, M. Davila,, G. J. Belsham, and, E. Domingo. 1993. A single nucleotide substitution in the internal ribosome entry site of foot-and-mouth disease virus leads to enhanced cap-independent translation in vivo. J. Virol. 67: 3748– 3755.
117. Matthews, D. A.,, P. S. Dragovich,, S. E. Webber,, S. A. Fuhrman,, A. K. Patick,, L. S. Zalman,, T. F. Hendrickson,, R. A. Love,, T. J. Prins,, J. T. Marakovits,, R. Zhou,, J. Tikhe,, C. E. Ford,, J. W. Meador,, R. A. Ferre,, E. L. Brown,, S. L. Binford,, M. A. Brothers,, D. M. DeLisle, and, S. T. Worland. 1999. Structure-assisted design of mechanism-based irreversible inhibitors of human rhinovirus 3C protease with potent antiviral activity against multiple rhinovirus serotypes. Proc. Natl. Acad. Sci. USA 96: 11000– 11007.
118. Matthews, D. A.,, W. W. Smith,, R. A. Ferre,, B. Condon,, G. Budahazi,, W. Sisson,, J. E. Villafranca,, C. A. Janson,, H. E. McElroy,, C. L. Gribskov, et al. 1994. Structure of human rhinovirus 3C protease reveals a trypsin-like polypeptide fold, RNA-binding site, and means for cleaving precursor polyprotein. Cell 77: 761– 771.
119. Mayer, C.,, D. Neubauer,, A. T. Nchinda,, R. Cencic,, K. Trompf, and, T. Skern. 2008. Residue L143 of the foot-and-mouth disease virus leader proteinase is a determinant of cleavage specificity. J. Virol. 82: 4656– 4659.
120. McLean, C.,, T. J. Matthews, and, R. R. Rueckert. 1976. Evidence of ambiguous processing and selective degradation in the noncapsid proteins of rhinovirus 1A. J. Virol. 19: 903– 914.
121. Medina, M.,, E. Domingo,, J. K. Brangwyn, and, G. J. Belsham. 1993. The two species of the foot-and-mouth disease virus leader protein, expressed individually, exhibit the same activities. Virology 194: 355– 359.
122. Merrill, M. K., and, M. Gromeier. 2006. The double-stranded RNA binding protein 76:NF45 heterodimer inhibits translation initiation at the rhinovirus type 2 internal ribosome entry site. J. Virol. 80: 6936– 6942.
123. Molla, A.,, K. S. Harris,, A. V. Paul,, S. H. Shin,, J. Mugavero, and, E. Wimmer. 1994. Stimulation of poliovirus proteinase 3C pro-related proteolysis by the genome-linked protein VPg and its precursor 3AB. J. Biol. Chem. 269: 27015– 27020.
124. Molla, A.,, S. K. Jang,, A. V. Paul,, Q. Reuer, and, E. Wimmer. 1992. Cardioviral internal ribosomal entry site is functional in a genetically engineered dicistronic poliovirus. Nature 356: 255– 257.
125. Monie, T. P.,, A. J. Perrin,, J. R. Birtley,, T. R. Sweeney,, I. Kara-kasiliotis,, Y. Chaudhry,, L. O. Roberts,, S. Matthews,, I. G. Goodfellow, and, S. Curry. 2007. Structural insights into the transcriptional and translational roles of Ebp1. EMBO J. 26: 3936– 3944.
126. Mosimann, S. C.,, M. M. Cherney,, S. Sia,, S. Plotch, and, M. N. James. 1997. Refined X-ray crystallographic structure of the poliovirus 3C gene product. J. Mol. Biol. 273: 1032– 1047.
127. Nadal, A.,, M. Martell,, J. R. Lytle,, A. J. Lyons,, H. D. Robertson,, B. Cabot,, J. I. Esteban,, R. Esteban,, J. Guardia, and, J. Gomez. 2002. Specific cleavage of hepatitis C virus RNA genome by human RNase P. J. Biol. Chem. 277: 30606– 30613.
128. Neubauer, D.,, J. Steinberger and, T. Skern. 2009. Picornaviruses. In U. Lendeckel and, N. M. Hooper (ed.), Viral Proteases and Antiviral Protease Inhibitor Therapy. Proteases in Biology and Disease, vol. 8. Springer, New York, NY.
129. Newman, J. F., and, F. Brown. 1997. Foot-and-mouth disease virus and poliovirus particles contain proteins of the replication complex. J. Virol. 71: 7657– 7662.
130. Ohlenschlager, O.,, J. Wohnert,, E. Bucci,, S. Seitz,, S. Hafner,, R. Ramachandran,, R. Zell, and, M. Gorlach. 2004. The structure of the stem-loop D subdomain of coxsackievirus B3 clover-leaf RNA and its interaction with the proteinase 3C. Structure 12: 237– 248.
131. Orlova, M.,, A. Yueh,, J. Leung, and, S. P. Goff. 2003. Reverse transcriptase of Moloney murine leukemia virus binds to eukaryotic release factor 1 to modulate suppression of translational termination. Cell 115: 319– 331.
132. Pacheco, A.,, S. Lopez de Quinto,, J. Ramajo,, N. Fernandez, and, E. Martinez-Salas. 2009. A novel role for Gemin5 in mRNA translation. Nucleic Acids Res. 37: 582– 590.
133. Pacheco, A.,, S. Reigadas, and, E. Martinez-Salas. 2008. Riboproteomic analysis of polypeptides interacting with the internal ribosome-entry site element of foot-and-mouth disease viral RNA. Proteomics 8: 4782– 4790.
134. Pallansch, M. A.,, O. M. Kew,, B. L. Semler,, D. R. Omilianowski,, C. W. Anderson,, E. Wimmer, and, R. R. Rueckert. 1984. Protein processing map of poliovirus. J. Virol. 49: 873– 880.
135. Palmenberg, A. C.,, M. A. Pallansch, and, R. R. Rueckert. 1979. Protease required for processing picornaviral coat protein resides in the viral replicase gene. J. Virol. 32: 770– 778.
136. Palmenberg, A. C.,, G. D. Parks,, D. J. Hall,, R. H. Ingraham,, T. W. Seng, and, P. V. Pallai. 1992. Proteolytic processing of the cardioviral P2 region: primary 2A/2B cleavage in clone-derived precursors. Virology 190: 754– 762.
137. Parks, G. D.,, J. C. Baker, and, A. C. Palmenberg. 1989. Proteolytic cleavage of encephalomyocarditis virus capsid region substrates by precursors to the 3C enzyme. J. Virol. 63: 1054– 1058.
138. Pelham, H. R. 1978. Translation of encephalomyocarditis virus RNA in vitro yields an active proteolytic processing enzyme. Eur. J. Biochem. 85: 457– 462.
139. Pelletier, J., and, N. Sonenberg. 1988. Internal initiation of translation of eukaryotic mRNA directed by a sequence derived from poliovirus RNA. Nature 334: 320– 325.
140. 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: 8919– 8932.
141. Pestova, T. V.,, C. U. Hellen, and, I. N. Shatsky. 1996. Canonical eukaryotic initiation factors determine initiation of translation by internal ribosomal entry. Mol. Cell. Biol. 16: 6859– 6869.
142. Pestova, T. V.,, I. N. Shatsky,, S. P. Fletcher,, R. J. Jackson, and, C. U. Hellen. 1998. A prokaryotic-like mode of cytoplasmic eukaryotic ribosome binding to the initiation codon during internal translation initiation of hepatitis C and classical swine fever virus RNAs. Genes Dev. 12: 67– 83.
143. Peters, H.,, Y. Y. Kusov,, S. Meyer,, A. J. Benie,, E. Bauml,, M. Wolff,, C. Rademacher,, T. Peters, and, V. Gauss-Muller. 2005. Hepatitis A virus proteinase 3C binding to viral RNA: correlation with substrate binding and enzyme dimerization. Biochem. J. 385: 363– 370.
144. Petersen, J. F.,, M. M. Cherney,, H. D. Liebig,, T. Skern,, E. Kuechler, and, M. N. James. 1999. The structure of the 2A proteinase from a common cold virus: a proteinase responsible for the shut-off of host-cell protein synthesis. EMBO J. 18: 5463– 5475.
145. Phelan, M.,, R. J. Banks,, G. Conn, and, V. Ramesh. 2004. NMR studies of the structure and Mg 2+ binding properties of a conserved RNA motif of EMCV picornavirus IRES element. Nucleic Acids Res. 32: 4715– 4724.
146. Piccone, M. E.,, E. Rieder,, P. W. Mason, and, M. J. Grubman. 1995. The foot-and-mouth disease virus leader proteinase gene is not required for viral replication. J. Virol. 69: 5376– 5382.
148. Pilipenko, E. V.,, E. G. Viktorova,, S. T. Guest,, V. I. Agol, and, R. P. Roos. 2001. Cell-specific proteins regulate viral RNA translation and virus-induced disease. EMBO J. 20: 6899– 6908.
149. Pisarev, A. V.,, L. S. Chard,, Y. Kaku,, H. L. Johns,, I. N. Shatsky, and, G. J. Belsham. 2004. Functional and structural similarities between the internal ribosome entry sites of hepatitis C virus and porcine teschovirus, a picornavirus. J. Virol. 78: 4487– 4497.
150. Ramos, R., and, E. Martinez-Salas. 1999. Long-range RNA interactions between structural domains of the aphthovirus internal ribosome entry site (IRES). RNA 5: 1374– 1383.
151. Roberts, P. J., and, G. J. Belsham. 1995. Identification of critical amino acids within the foot-and-mouth disease virus leader protein, a cysteine protease. Virology 213: 140– 146.
152. Robertson, M. E.,, R. A. Seamons, and, G. J. Belsham. 1999. A selection system for functional internal ribosome entry site (IRES) elements: analysis of the requirement for a conserved GNRA tetraloop in the encephalomyocarditis virus IRES. RNA 5: 1167– 1179.
153. Rodriguez Pulido, M.,, P. Serrano,, M. Saiz, and, E. Martinez-Salas. 2007. Foot-and-mouth disease virus infection induces proteolytic cleavage of PTB, eIF3A, B, and PABP RNA-binding proteins. Virology 364: 466– 474.
154. Roos, R. P.,, W. P. Kong, and, B. L. Semler. 1989. Polyprotein processing of Theiler’s murine encephalomyelitis virus. J. Virol. 63: 5344– 5353.
155. Rueckert, R. R.,, T. J. Matthews,, O. M. Kew,, M. A. Pallansch,, C. McLean and, D. R. Omilianowski. 1979. Synthesis and processing of picornaviral polyprotein, p. 113–125. In R. Perez-Bercoff (ed.), The Molecular Biology of Picornaviruses, vol. 6. Plenum, New York, NY.
156. Ryan, M. D.,, G. J. Belsham, and, A. M. King. 1989. Specificity of enzyme-substrate interactions in foot-and-mouth disease virus polyprotein processing. Virology 173: 35– 45.
157. Ryan, M. D., and, J. Drew. 1994. Foot-and-mouth disease virus 2A oligopeptide mediated cleavage of an artificial polyprotein. EMBO J. 13: 928– 933.
158. Ryan, M. D., and, M. Flint. 1997. Virus-encoded protein-ases of the picornavirus super-group. J. Gen. Virol. 78: 699– 723.
159. Ryan, M. D.,, A. M. King, and, G. P. Thomas. 1991. Cleavage of foot-and-mouth disease virus polyprotein is mediated by residues located within a 19 amino acid sequence. J. Gen. Virol. 72: 2727– 2732.
160. Saiz, M.,, S. Gomez,, E. Martinez-Salas, and, F. Sobrino. 2001. Deletion or substitution of the aphthovirus 3′ NCR abrogates infectivity and virus replication. J. Gen. Virol. 82: 93– 101.
161. Santos, J. A.,, I. E. Gouvea,, W. A. Judice,, M. A. Izidoro,, F. M. Alves,, R. L. Melo,, M. A. Juliano,, T. Skern, and, L. Juliano. 2009. Hydrolytic properties and substrate specificity of the foot-and-mouth disease leader protease. Biochemistry 48: 7948– 7458.
162. Schultheiss, T.,, Y. Y. Kusov, and, V. Gauss-Muller. 1994. Proteinase 3C of hepatitis A virus (HAV) cleaves the HAV polyprotein P2-P3 at all sites including VP1/2A and 2A/2B. Virology 198: 275– 281.
163. Seipelt, J.,, A. Guarne,, E. Bergmann,, M. James,, W. Sommergruber,, I. Fita, and, T. Skern. 1999. The structures of picornaviral proteinases. Virus Res. 62: 159– 168.
164. Serrano, P.,, J. Gomez, and, E. Martinez-Salas. 2007. Characterization of a cyanobacterial RNase P ribozyme recognition motif in the IRES of foot-and-mouth disease virus reveals a unique structural element. RNA 13: 849– 859.
165. Serrano, P.,, M. R. Pulido,, M. Saiz, and, E. Martinez-Salas. 2006. The 3′ end of the foot-and-mouth disease virus genome establishes two distinct long-range RNA-RNA interactions with the 5′ end region. J. Gen. Virol. 87: 3013– 3022.
166. Serrano, P.,, J. Ramajo, and, E. Martinez-Salas. 2009. Rescue of internal initiation of translation by RNA complementation provides evidence for a distribution of functions between individual IRES domains. Virology 388: 221– 229.
167. Silverman, R. H. 2007. Viral encounters with 2′, 5′-oligoadenylate synthetase and RNase L during the interferon antiviral response. J. Virol. 81: 12720– 12729.
168. Skern, T.,, B. Hampölz,, A. Guarné,, I. Fita,, E. Bergmann,, J. Petersen, and, M. N. G. James. 2002. Structure and function of picornavirus proteinases, p. 199–212. In B. L. Semler and, E. Wimmer (ed.), Molecular Biology of Picornaviruses. ASM Press, Washington, DC.
169. Skern, T.,, I. Fita, and, A. Guarne. 1998. A structural model of picornavirus leader proteinases based on papain and bleomycin hydrolase. J. Gen. Virol. 79: 301– 307.
170. Skern, T.,, W. Sommergruber,, H. Auer,, P. Volkmann,, M. Zorn,, H. D. Liebig,, F. Fessl,, D. Blaas, and, E. Kuechler. 1991. Substrate requirements of a human rhinoviral 2A proteinase. Virology 181: 46– 54.
171. Skinner, M. A.,, V. R. Racaniello,, G. Dunn,, J. Cooper,, P. D. Minor, and, J. W. Almond. 1989. New model for the secondary structure of the 5′ non-coding RNA of poliovirus is supported by biochemical and genetic data that also show that RNA secondary structure is important in neurovirulence. J. Mol. Biol. 207: 379– 392.
172. Sommergruber, W.,, G. Casari,, F. Fessl,, J. Seipelt, and, T. Skern. 1994. The 2A proteinase of human rhinovirus is a zinc containing enzyme. Virology 204: 815– 818.
173. Sommergruber, W.,, J. Seipelt,, F. Fessl,, T. Skern,, H. D. Liebig, and, G. Casari. 1997. Mutational analyses support a model for the HRV2 2A proteinase. Virology 234: 203– 214.
174. Sommergruber, W.,, M. Zorn,, D. Blaas,, F. Fessl,, P. Volkmann,, I. Maurer-Fogy,, P. Pallai,, V. Merluzzi,, M. Matteo,, T. Skern, et al. 1989. Polypeptide 2A of human rhinovirus type 2: identification as a protease and characterization by mutational analysis. Virology 169: 68– 77.
175. Song, Y.,, E. Tzima,, K. Ochs,, G. Bassili,, H. Trusheim,, M. Linder,, K. T. Preissner, and, M. Niepmann. 2005. Evidence for an RNA chaperone function of polypyrimidine tract-binding protein in picornavirus translation. RNA 11: 1809– 1824.
176. Sousa, C.,, E. M. Schmid, and, T. Skern. 2006. Defining residues involved in human rhinovirus 2A proteinase substrate recognition. FEBS Lett. 580: 5713– 5717.
177. Stone, J. K.,, R. Rijnbrand,, D. A. Stein,, Y. Ma,, Y. Yang,, P. L. Iversen, and, R. Andino. 2008. A morpholino oligomer targeting highly conserved internal ribosome entry site sequence is able to inhibit multiple species of picornavirus. Antimicrob. Agents Chemother. 52: 1970– 1981.
178. Strebel, K., and, E. Beck. 1986. A second protease of foot-and-mouth disease virus. J. Virol. 58: 893– 899.
179. Summers, D. F., and, J. V. Maizel, Jr. 1968. Evidence for large precursor proteins in poliovirus synthesis. Proc. Natl. Acad. Sci. USA 59: 966– 971.
180. Summers, D. F.,, E. N. Shaw,, M. L. Stewart, and, J. V. Maizel, Jr. 1972. Inhibition of cleavage of large poliovirus-specific precursor proteins in infected HeLa cells by inhibitors of proteolytic enzymes. J. Virol. 10: 880– 884.
181. Svitkin, Y. V., and, V. I. Agol. 1983. Translational barrier in central region of encephalomyocarditis virus genome. Modulation by elongation factor 2 (eEF-2). Eur. J. Biochem. 133: 145– 154.
182. Svitkin, Y. V.,, A. Pause,, A. Haghighat,, S. Pyronnet,, G. Wither-ell,, G. J. Belsham, and, N. Sonenberg. 2001. The requirement for eukaryotic initiation factor 4A (elF4A) in translation is in direct proportion to the degree of mRNA 5′ secondary structure. RNA 7: 382– 394.
183. Sweeney, T. R.,, N. Roque-Rosell,, J. R. Birtley,, R. J. Leather-barrow, and, S. Curry. 2007. Structural and mutagenic analysis of foot-and-mouth disease virus 3C protease reveals the role of the beta-ribbon in proteolysis. J. Virol. 81: 115– 124.
184. Toyoda, H.,, M. J. Nicklin,, M. G. Murray,, C. W. Anderson,, J. J. Dunn,, F. W. Studier, and, E. Wimmer. 1986. A second virus-encoded proteinase involved in proteolytic processing of poliovirus polyprotein. Cell 45: 761– 770.
185. Vakharia, V. N.,, M. A. Devaney,, D. M. Moore,, J. J. Dunn, and, M. J. Grubman. 1987. Proteolytic processing of foot-and-mouth disease virus polyproteins expressed in a cell-free system from clone-derived transcripts. J. Virol. 61: 3199– 3207.
186. Voss, T.,, R. Meyer, and, W. Sommergruber. 1995. Spectroscopic characterization of rhinoviral protease 2A: Zn is essential for the structural integrity. Protein Sci. 4: 2526– 2531.
187. Walker, P. A.,, L. E. Leong, and, A. G. Porter. 1995. Sequence and structural determinants of the interaction between the 5′-noncoding region of picornavirus RNA and rhinovirus protease 3C. J. Biol. Chem. 270: 14510– 14516.
188. Walter, B. L.,, J. H. Nguyen,, E. Ehrenfeld, and, B. L. Semler. 1999. Differential utilization of poly(rC) binding protein 2 in translation directed by picornavirus IRES elements. RNA 5: 1570– 1585.
189. Yamasaki, K.,, C. C. Weihl, and, R. P. Roos. 1999. Alternative translation initiation of Theiler’s murine encephalomyelitis virus. J. Virol. 73: 8519– 8526.
190. Ypma-Wong, M. F.,, P. G. Dewalt,, V. H. Johnson,, J. G. Lamb, and, B. L. Semler. 1988. Protein 3CD is the major poliovirus proteinase responsible for cleavage of the P1 capsid precursor. Virology 166: 265– 270.
191. Ypma-Wong, M. F.,, D. J. Filman,, J. M. Hogle, and, B. L. Semler. 1988. Structural domains of the poliovirus polyprotein are major determinants for proteolytic cleavage at Gln-Gly pairs. J. Biol. Chem. 263: 17846– 17856.
192. Yu, S. F., and, R. E. Lloyd. 1992. Characterization of the roles of conserved cysteine and histidine residues in poliovirus 2A protease. Virology 186: 725– 735.
193. Yu, S. F., and, R. E. Lloyd. 1991. Identification of essential amino acid residues in the functional activity of poliovirus 2A protease. Virology 182: 615– 625.
194. Zell, R.,, K. Sidigi,, E. Bucci,, A. Stelzner, and, M. Gorlach. 2002. Determinants of the recognition of enteroviral clover-leaf RNA by coxsackievirus B3 proteinase 3C. RNA 8: 188– 201.
195. Zha, J.,, S. Weiler,, K. J. Oh,, M. C. Wei, and, S. J. Korsmeyer. 2000. Posttranslational N-myristoylation of BID as a molecular switch for targeting mitochondria and apoptosis. Science 290: 1761– 1765.
196. Zhou, A.,, J. M. Paranjape,, B. A. Hassel,, H. Nie,, S. Shah,, B. Galinski, and, R. H. Silverman. 1998. Impact of RNase L overexpression on viral and cellular growth and death. J. Interferon Cytokine Res. 18: 953– 961.

References: V. 
 V. 
 V. 
 V. 
 V. 
 V. 
 V. 
 V. 
 V. 
 V. 
 V. 
 V. 
 V. 
 V. 
 V. 
 V. 
 V. 
 V. 
 V. 
 V. 
 V. 
 V. 
 V. 
 V. 
 V. 
 V. 
 V. 
 V. 
 V. 
 V. 
 V. 
 V. 
 V. 
 V. 
 V. 
 V. 
 V.