Chapter 5 : Translation and Host Cell Shutoff

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Poliovirus represents the prototypic enterovirus, and thus, much of the information available on the mechanism of protein synthesis of enteroviruses has been derived from its study. The other members of the genus , such as coxsackieviruses A and B and enteric cytopathic human orphan (ECHO) virus, presumably display similar modes of translation initiation. Enteroviruses, like all members of the family, have a positive-sense (i.e., message-sense), single-stranded RNA genome that is translated in the cellular cytoplasm immediately after the virions have been uncoated. Enteroviral RNAs resemble cellular mRNAs to such an extent that the viral mRNAs are translated efficiently by the host cell translation machinery, although the mechanism for initiation of protein synthesis appears to be distinct from that employed for most eukaryotic mRNAs. In poliovirus-infected cells, eIF-4F is targeted for proteolysis, thereby causing a shutoff of host cell translation, but the processed form of eIF-4F is still capable of stimulating poliovirus protein synthesis.

Citation: Haller A, Semler B. 1995. Translation and Host Cell Shutoff, p 113-133. In Rotbart H (ed), Human Enterovirus Infections. ASM Press, Washington, DC. doi: 10.1128/9781555818326.ch5

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Theiler's Murine Encephalomyelitis
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Image of FIGURE 1

Diagram of computer-predicted secondary structure of the 5′ NCR of poliovirus RNA. This structure has been confirmed, in part, by RNase and chemical probing experiments. Numbers refer to the poliovirus type 1 RNA genome. The seven stem-loop structures are labeled A through G.An alternative nomenclature employing roman numerals for the stem-loop structures is indicated in parentheses ( ). In addition, Andino et al. ( ) suggested that stem-loops A and B form a cloverleaf structure. This structure would compose the I stem-loop region shown in the figure. The asterisks indicate AUGs conserved among the enteroviruses and rhinoviruses. The conserved polypyrimidine tract (UUUCCUU) is located at nt 558 to 577; the conserved AUG at position 586 is indicated. The AUG at nt 743 represent the authentic translation start codon. The figure is modified from that of Dildine and Semler ( ).

Citation: Haller A, Semler B. 1995. Translation and Host Cell Shutoff, p 113-133. In Rotbart H (ed), Human Enterovirus Infections. ASM Press, Washington, DC. doi: 10.1128/9781555818326.ch5
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Image of FIGURE 2

Diagram of bicistronic mRNAs directing cap-independent translation initiation in uninfected and poliovirus-infected cells. The bicistronic RNA consists of a capped mRNA encoding TK that is fused to the poliovirus 5′ NCR linked to the second cistron encoding CAT. In uninfected cells, the capped mRNA encoding TK is translated in a cap-dependent manner. Translation of the second cistron encoding CAT could occur in two ways: by ribosomal readthrough and reinitiation of ribosomes that bound at the 5′ end of the bicistronic mRNA or by internal ribosome entry in the 5′ NCR of poliovirus. In poliovirus-infected cells, cap-dependent translation initiation is inhibited by the proteolytic processing of translation initiation factor eIF-4F. Thus, no TK protein is observed. However, the CAT mRNA is still translated, presumably by ribosomes binding internally at the IRES element within the 5′ NCR of poliovirus RNA. Reprinted with permission from ( ). © 1988 Macmillan Magazines Limited.

Citation: Haller A, Semler B. 1995. Translation and Host Cell Shutoff, p 113-133. In Rotbart H (ed), Human Enterovirus Infections. ASM Press, Washington, DC. doi: 10.1128/9781555818326.ch5
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Image of FIGURE 3

Diagram of conserved sequence elements in the IRES of enteroviral RNAs. The conserved sequence elements, i.e., the polypyrimidine tract and the upstream AUG codon (at nt 586 in poliovirus type 1), are boxed. The AUG codon is present in stem-loop G of the 5′ NCR of enterovirus RNA. The nucleotide sequences of the AUG codon are predicted to be base paired in a stem structure. A distance of 20 nt between the pyrimidine-rich region and the AUG at nt 586 is required for efficient translation initiation by internal ribosome entry on viral RNAs. Stem-loop G sequences are followed by a region of viral RNA that is not well conserved among the enteroviruses (the variable region). The authentic translation start codon is located at nt 743 and is thus ∼150 nt downstream of the polypyrimidine tract. This AUG codon may be located by ribosome scanning of the viral RNA.

Citation: Haller A, Semler B. 1995. Translation and Host Cell Shutoff, p 113-133. In Rotbart H (ed), Human Enterovirus Infections. ASM Press, Washington, DC. doi: 10.1128/9781555818326.ch5
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Image of FIGURE 4

Kinetics of protein synthesis in poliovirus-infected cells compared to the rate of protein synthesis in uninfected cells. By approximately 2 h postinfection, cap-dependent cellular protein synthesis has ceased in infected cells. By 3.5 to 4 h postinfection, cap-independent virus-specific protein synthesis occurs at high levels. In uninfected cells, continuous cellular protein synthesis is observed. (Adapted from reference with permission.)

Citation: Haller A, Semler B. 1995. Translation and Host Cell Shutoff, p 113-133. In Rotbart H (ed), Human Enterovirus Infections. ASM Press, Washington, DC. doi: 10.1128/9781555818326.ch5
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Image of FIGURE 5

Models of shutoff of host cell protein synthesis for poliovirus and coxsackievirus. In poliovirus-infected cells, a latent cellular protease is activated by the viral 2A, perhaps by proteolysis. The cellular protease carries out the cleavage of p220, a component of eIF-4F, in the presence of eIF-3, resulting in inactive eIF-4F and an inhibition of cap-dependent translation initiation. In contrast, the coxsackievirus 2A can carry out p220 cleavage itself without a requirement for eIF-3.

Citation: Haller A, Semler B. 1995. Translation and Host Cell Shutoff, p 113-133. In Rotbart H (ed), Human Enterovirus Infections. ASM Press, Washington, DC. doi: 10.1128/9781555818326.ch5
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1. Ambros, V.,, and D. Baltimore. 1978. Protein is linked to the 5' end of poliovirus RNA by phosphodiester linkage to tyrosine. J. Biol. Chem. 253:52635266.
2. Andino, R.,, G. E. Rieckhof,, and D. Baltimore. 1990. A functional ribonucleoprotein complex forms around the 5' end of poliovirus RNA. Cell 63:369380.
3. Anthony, D. D.,, and W. C. Merrick. 1991. Eukaryotic initiation factor (eIF)-4F: implications for a role in internal initiation of translation. J. Biol. Chem. 266:1021810226.
4. Bernstein, H. D.,, N. Sonenberg,, and D. Baltimore. 1985. Poliovirus mutant that does not selectively inhibit host cell protein synthesis. Mol. Cell. Biol. 5:29132923.
5. Bienkowska-Szewczyk, K.,, and E. Ehrenfeld. 1988. An internal 5'-noncoding region required for translation of poliovirus RNA in vitro. J. Virol. 62:30683072.
6. 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: 3948.
7. Bonneau, A.-M.,, and N. Sonenberg. 1987. Proteolysis of the p220 component of the cap-binding protein complex is not sufficient for complete inhibition of host cell protein synthesis after poliovirus infection. J. Virol. 61:986991.
8. Borman, A.,, M. T. Howell,, J. G. Patton,, and R. J. Jackson. 1993. The involvement of a spliceosome component in internal initiation of human rhinovirus RNA translation. J. Gen. Virol. 74:17751788.
9. Brown, B. A.,, and E. Ehrenfeld. 1979. Translation of poliovirus RNA in vitro: changes in cleavage pattern and initiation sites by ribosomal salt wash. Virology 97:396405.
10. Buckley, B.,, and E. Ehrenfeld. 1987. The cap-binding protein complex in uninfected and poliovirus-infected HeLa cells. J. Biol. Chem. 262:1359913606.
11. Clark, M.,, and A. Dasgupta. 1990. A transcriptionally active form of TFIIIC is modified in poliovirus-infected HeLa cells. Mol. Cell. Biol. 10:51065113.
12. Clark, M.,, T. Haemmerle,, E. Wimmer,, and A. Dasgupta. 1991. Poliovirus proteinase 3C converts an active form of transcription factor IIIC to an inactive form: a mechanism for inhibition of host cell polymerase III transcription by poliovirus. EMBO J. 10:29412947.
13. Clark, M. E.,, P. M. Lieberman,, A. J. Berk,, and A. Dasgupta. 1993. Direct cleavage of human TATA-binding protein by poliovirus protease 3C in vivo and in vitro. Mol. Cell. Biol. 13:12321237.
14. Crawford, N.,, A. Fire,, M. Samuels,, P. A. Sharp,, and D. Baltimore. 1981. Inhibition of transcription factor activity by poliovirus. Cell 27:555561.
15. Davies, M. V.,, J. Pelletier,, K. Meerovitch,, N. Sonenberg,, and R.J. Kaufman. 1991. The effect of poliovirus proteinase 2Apro expression on cellular metabolism. J. Biol. Chem. 266:1471414720.
16. Devaney, M. A.,, V. N. Vakharia,, R. E. Lloyd,, E. Ehrenfeld,, and M. J. Grubman. 1988. Leader protein of foot-and-mouth disease virus is required for cleavage of the p220 component of the cap-binding protein complex. J. Virol. 62:44074409.
17. Dildine, S. L.,, and B. L. Semler. 1989. The deletion of 41 proximal nucleotides reverts a poliovirus mutant containing a temperature-sensitive lesion in the 5' noncoding region of genomic RNA. J. Virol. 63:847862.
18. Dildine, S. L.,, and B. L. Semler. 1992. Conservation of RNA-protein interactions among picornaviruses. J. Virol. 66:43644376.
19. Dildine, S. L.,, K. R. Stark,, A. A. Haller,, and B. L. Semler. 1991. Poliovirus translation initiation: differential effects of directed and selected mutations in the 5' noncoding region of viral RNAs. Virology 182:742752.
20. Dorner, A. J.,, L. F. Dorner,, G. R. Larsen,, E. Wimmer,, and C. W. Anderson. 1982. Identification of the initiation site of poliovirus polyprotein synthesis. J. Virol. 42:10171028.
21. Dorner, A. J.,, B. L. Semler,, R. J. Jackson,, R. Hanecak,, E. Duprey,, and E. Wimmer. 1984. In vitro translation of poliovirus RNA: utilization of internal initiation sites in reticulocyte lysate. J. Virol. 50:507514.
22. Ehrenfeld, E., 1984. Picornavirus inhibition of host cell protein synthesis, p. 177221. In H. Fraenkel-Conrat, and R. R. Wagner (ed.), Comprehensive Virology, vol. 19. Plenum Press, New York.
23. Etchison, D.,, S. Milburn,, I. Edery,, N. Sonenberg,, and J. W. B. Hershey. 1982. Inhibition of HeLa cell protein synthesis following poliovirus infection correlates with the proteolysis of a 220,000 dalton polypeptide associated with eucaryotic initiation factor 3 and a cap binding protein complex. J. Biol. Chem. 257:1480614810.
24. Etchison, D. S.,, J. Hansen,, E. Ehrenfeld,, I. Edery,, N. Sonenberg,, S. Milburn,, and J. W. B. Hershey. 1984. Demonstration in vitro that eucaryotic initiation factor 3 is active but that a cap-binding protein complex is inactive in poliovirus-infected cells. J. Virol. 51:832837.
25. Fradkin, L. G.,, S. K. Yoshinaga,, A. J. Berk,, and A. Dasgupta. 1987. Inhibition of host cell RNA polymerase Ill-mediated transcription by poliovirus: inactivation of specific transcription factors. Mol. Cell Biol. 7:38803887.
26. Garcia-Blanco, M. A.,, S. F. Jamison,, and P. A. Sharp. 1989. Identification and purification of a 62,000-dalton protein that binds specifically to the polypyrimidine tract of in-trons. Genes Dev. 3:18741886.
27. Gebhard, J. R.,, and E. Ehrenfeld. 1992. Specific interactions of HeLa cell proteins with proposed translation domains of the poliovirus 5' noncoding region. J. Virol. 66:31013109.
28. Ghetti, A.,, S. Piol-Roma,, W. M. Michael,, C. Morandi,, and G. Dreyfuss. 1992. hnRNP I, the polypyrimidine tract-binding protein: distinct nuclear localization and association with hn RNAs. Nucleic Acids Res. 20:36713678.
29. Gmyl, A. P.,, E. V. Pilipenko,, S. V. Maslova,, G. A. Belov,, and V. I. Agol. 1993. Functional and genetic plasticities of the poliovirus genome: quasi-infectious RNAs modified in the 5'-untranslated region yield a variety of pseudorevertants. J. Virol. 67:63096316.
30. Golini, F.,, B. L. Semler,, A. J. Dorner,, and E. Wimmer. 1980. Protein-linked RNA of poliovirus is competent to form an initiation complex of translation in vitro. Nature (London) 287:600603.
31. Gorbalenya, A. E.,, E. V. Koonin,, and M. M.-C. 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. 288:201205.
32. Haller, A. A.,, J. H. C. Nguyen,, and B. L. Semler. 1993. Minimum internal ribosome entry site required for poliovirus infectivity. J. Virol. 67:74617471.
33. Haller, A. A.,, and B. L. Semler. 1992. Linker scanning mutagenesis of the internal ribosome entry site of poliovirus RNA. J. Virol. 66:50755086.
34. Haller, A. A.,, and B. L. Semler. Stem-loop structure synergy in binding cellular proteins to the 5' noncoding region of poliovirus RNA. Virology, in press.
35. Hambidge, S. J.,, and P. Sarnow. 1992. Translational enhancement of the poliovirus 5' noncoding region mediated by virus-encoded polypeptide 2A. Proc. Natl. Acad. Sci. USA 89:1027210276.
36. Harber, J.,, and E. Wimmer,. 1993. Aspects of the molecular biology of picornaviruses, p. 189224. In L. Carrasco,, N. Sonenberg,, and E. Wimmer (ed.), Regulation of Gene Expression in Animal Viruses. Plenum Press, New York.
37. Hellen, C. U. T.,, M. Faecke,, H.-G. Kraeusslich,, 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. 65:42264231.
38. Hellen, C. U. T.,, T. V. Pestova,, M. Litterst,, and E. Wimmer. 1994. The cellular polypeptide p57 (pyrimidine tract-binding protein) binds to multiple sites in the poliovirus 5' nontranslated region. J. Virol. 68:941950.
39. Hellen, C. U. T.,, G. W. Witherell,, M. Schmid,, S. H. Shin,, T. V. Pestova,, A. Gil,, and E. Wimmer. 1993. A cytoplasmic 57 kDa protein (p57) that is required for translation of picornavirus RNA by internal ribosome entry is identical to the nuclear polypyrimidine tract-binding protein. Proc. Natl. Acad. Sci. USA 90:76427646.
40. Holland, J. J. 1962. Inhibition of DNA-primed RNA synthesis during poliovirus infection of human cells. Biochem. Biophys. Res. Commun. 9:556573.
41. Iizuka, N.,, M. Kohara,, K. Hagino-Yamagishi,, S. Abe,, T. Komatsu,, K. Tago,, M. Arita,, and A. Nomoto. 1989. Construction of less neurovirulent polioviruses by introducing deletions into the 5' noncoding sequence of the genome. J. Virol. 63:53545363.
42. Iizuka, N.,, H. Yonekawa,, and A. Nomoto. 1991. Nucleotide sequences important for translation initiation of enterovirus RNA. J. Virol. 65:48674873.
43. Jackson, R. J.,, M. T. Howell,, and A. Kaminski. 1990. The novel mechanism of initiation of picornavirus RNA translation. Trends Biochem. Sci. 15:477483.
44. Jacobson, S. J.,, D. A. M. Konings,, and P. Sarnow. 1993. Biochemical and genetic evidence for a pseudoknot structure at the 3' terminus of the poliovirus RNA genome and its role in viral RNA amplification. J. Virol. 67:29612971.
45. Jang, S. K.,, H. G. Krausslich,, M. J. H. Nicklin,, G. M. Duke,, A. C. Palmenberg,, and E. Wimmer. 1988. A segment of the 5' untranslated region of encephalomyelitis virus RNA directs internal entry of ribosomes during in vitro translation. J. Virol. 62:26362643.
46. Jang, S. K.,, T. V. Pestova,, C. U. T. Hellen,, G. W. Witherell,, and E. Wimmer. 1990. Cap-independent translation of picornavirus RNAs: structure and function of the internal ribosomal entry site. Enzyme 44:292309.
47. Joachims, M.,, and D. Etchison. 1992. Poliovirus infection results in structural alteration of a microtubule-associated protein. J. Virol. 66:57975804.
48. Johnson, V. H.,, and B. L. Semler. 1988. Defined recombinants of poliovirus and coxsackievirus: sequence-specific deletions and functional substitutions in the 5'-noncoding regions of viral RNAs. Virology 162:4757.
49. Kaminski, A.,, T. Howell,, and R. J. Jackson. 1990. Initiation of encephalomyocarditis virus RNA translation: the authentic initiation site is not selected by a scanning mechanism. EMBO J. 9:37533759.
50. Kenan, D. J.,, C. C. Query,, and J. D. Keene. 1991. RNA recognition: towards identifying determinants of specificity. Trends Biochem. Sci. 16:214220.
51. Kitamura, N.,, B. L. Semler,, P. G. Rothberg,, G. R. Larsen,, C. J. Adler,, A. J. Dorner,, E. A. Emini,, R. Hanecak,, J. J. Lee,, S. van der Werf,, C. W. Anderson,, and E. Wimmer. 1981. Primary structure, gene organization, and polypeptide expression of poliovirus RNA. Nature (London) 291:547553.
52. Kleina, L. G.,, and M. J. Grubman. 1992. Antiviral effects of a thiol protease inhibitor on foot-and-mouth disease virus. J. Virol. 66:71687175.
53. Kliewer, S.,, C. Muchardt,, R. Gaynor,, and A. Dasgupta. 1990. Loss of a phosphorylated form of transcription factor CREB/ATF in poliovirus-infected cells. J. Virol. 64:45074515.
54. Kozak, M. 1989. The scanning model for translation: an update J. Cell Biol. 108:229241.
55. Kozak, M. 1991. Structural features in eukaryotic mRNAs that modulate the initiation of translation. J. Biol. Chem. 266:1986719870.
56. Kraeusslich, H. G.,, M. J. H. Nicklin,, H. Toyoda,, D. Etchison,, and E. Wimmer. 1987. Poliovirus proteinase 2A induces cleavage of eukaryotic initiation factor 4F polypeptide p220. J. Virol. 61:27112718.
57. Kuge, S.,, N. Kawamura,, and A. Nomoto. 1989. Genetic variation occurring in the genome of an in vitro insertion mutant of poliovirus type 1. J. Virol. 63:10691075.
58. La Monica, N.,, and V. R. Racaniello. 1989. Differences in replication of attenuated and neurovirulent polioviruses in human neuroblastoma cell line SH-SY5Y. J. Virol. 63:23572360.
59. Lampheart, B. J.,, R. Yan,, F. Yang,, D. Waters,, H.-D. Liebig,, H. Klump,, E. Kuechler,, T. Skern,, and R. E. Rhoads. 1993. Mapping the cleavage site in protein synthesis initiation factor eIF-4 gamma of the 2A proteases from human coxsackievirus. and rhinovirus. J. Biol. Chem. 268:1920019203.
60. Lawrence, C.,, and R. E. Thatch. 1974. Encephalomyocarditis virus infection of mouse plasmacytoma cells. J. Virol. 14:598610.
61. Le, S.-Y.,, and M. Zuker. 1990. Common structures of the 5' non-coding RNA in enteroviruses and rhinoviruses. J. Mol. Biol. 216:729741.
62. Lee, K. A. W.,, I. Edery,, R. Hanecak,, E. Wimmer,, and N. Sonenberg. 1985. Poliovirus protease 3C (P3-7c) does not cleave p220 of the eucaryotic mRNA cap-binding protein complex. J. Virol. 55:489493.
63. Lee, K. A. W.,, and N. Sonenberg. 1982. Inactivation of cap-binding proteins accompanies the shut-off of host protein synthesis by poliovirus. Proc. Natl. Acad. Sci. USA 79:34473451.
64. Liebig, H.-D.,, E. Ziegler,, R. Yan,, K. Hartmuth,, H. Klump,, H. Kowalski,, D. Blaas,, W. Sommergruber,, L. Frasel,, B. J. Lampheart,, R. E. Rhoads,, E. Kuechler,, and T. Skern. 1993. Purification of two picornaviral 2A proteinases: interaction with eIF-4 gamma and influence on in vitro translation. Biochemistry 32:75817588.
65. Linder, P.,, P. F. Lasko,, P. Leroy,, M. Ashburner,, P. Nielsen,, K. Nishi,, J. Schnier,, and P. P. Slonimski. 1989. Birth of the D-E-A-D box. Nature (London) 337:121122.
66. Lloyd, R. E.,, D. Etchison,, and E. Ehrenfeld. 1985. Poliovirus protease does not mediate cleavage of the 220,000-Da component of the cap binding protein complex. Proc. Natl. Acad. Sci. USA 82:27232727.
67. Lloyd, R. E.,, M. Grubman,, and E. Ehrenfeld. 1988. Relationship of p220 cleavage during picornavirus infection to 2A proteinase sequences. J. Virol. 62:42164223.
68. Lloyd, R. E.,, H. Toyoda,, D. Etchison,, E. Wimmer,, and E. Ehrenfeld. 1986. Cleavage of the cap binding protein complex polypeptide p220 is not effected by the second poliovirus protease 2A. Virology 150:299303.
69. Macadam, A. J.,, G. Ferguson,, T. Fleming,, D. M. Stone,, J. W. Almond,, and P. D. Minor. 1994. Role for poliovirus protease 2A in cap independent translation. EMBO J. 13:924927.
70. Macejak, D. G.,, and P. Sarnow. 1991. Internal initiation of translation mediated by the 5' leader of a cellular mRNA. Nature (London) 353:9094.
71. 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 194:355359.
72. Meerovitch, K.,, R. Nicholson,, and N. Sonenberg. 1991. In vitro mutational analysis of cis-acting RNA translational elements within the poliovirus type 2 5' untranslated region. J. Virol. 65:58955901.
73. Meerovitch, K.,, J. Pelletier,, and N. Sonenberg. 1989. A cellular protein that binds to the 5'-noncoding region of poliovirus RNA: implications for internal translation initiation. Genes Dev. 3:10261034.
74. Meerovitch, K.,, Y. U. Svitkin,, H. S. Lee,, F. Lejbkowicz,, D. J. Kenan,, E. K. L. Chan,, V. I. Agol,, J. D. Keene,, and N. Sonenberg. 1993. La autoantigen enhances and corrects aberrant translation of poliovirus RNA in reticulocyte lysate. J. Virol. 67:37983807.
75. Merrick, W. C. 1990. Overview: mechanism of translation initiation in eukaryotes. Enzyme 44:716.
76. Morris, D. R.,, T. Kakegawa,, R. L. Kaspar,, and M. W. White. 1993. Polypyrimidine tracts and their binding proteins: regulatory sites for posttranscriptional modulation of gene expression. Biochemistry 32:29312937.
77. Najita, L.,, and P. Sarnow. 1990. Oxidation-reduction sensitive interaction of a cellular 50-kD protein with an RNA hairpin in the 5' noncoding region of the poliovirus genome. Proc. Natl. Acad. Sci. USA 87:58465850.
78. Nicholson, R.,, J. Pelletier,, S. Le,, and N. Sonenberg. 1991. Structural and functional analysis of the ribosome landing pad of poliovirus type 2: in vivo translational studies. J. Virol. 65:58865894.
79. Nomoto, A.,, Y. F. Lee,, and E. Wimmer. 1976. The 5'-end of poliovirus mRNA is not capped with m7G(5')ppp(5')Np. Proc. Natl. Acad. Sci. USA 73:375380.
80. OH, S.-K.,, M. P. Scott,, and P. Sarnow. 1992. Homeotic gene Antennapedia mRNA contains 5'-noncoding sequences that confer translational initiation by internal ribosome binding. Genes Dev. 6:16431653.
81. Parks, G. D.,, G. M. Duke,, and A. C. Palmenberg. 1986. Encephalomyocarditis virus 3C protease: efficient cell-free expression from clones which link viral 5' noncoding sequences to the P3 region. J. Virol. 60:376384.
82. Patton, J. G.,, S. A. Mayer,, P. Tempst,, and B. Nadal-Ginard. 1991. Characterization and molecular cloning of polypyrimidine tract-binding protein: a component of a complex necessary for pre-mRNA splicing. Genes Dev. 5:12371251.
83. Pelletier, J.,, M. E. Flynn,, G. Kaplan,, V. Racaniello,, and N. Sonenberg. 1988. Mutational analysis of upstream AUG codons of poliovirus RNA. J. Virol. 62:44864492.
84. Pelletier, J.,, G. Kaplan,, V. R. Racaniello,, and N. Sonenberg. 1988. Cap-independent translation of poliovirus mRNA is conferred by sequence elements within the 5' noncoding region. Mol. Cell. Biol. 8:11031112.
85. Pelletier, J.,, and N. Sonenberg. 1988. Internal initiation of translation of eukaryotic mRNA directed by a sequence derived from poliovirus RNA. Nature (London) 334:320325.
86. Pelletier, J.,, and N. Sonenberg. 1989. Internal binding of eucaryotic ribosomes on poliovirus RNA: translation in HeLa cell extracts. J. Virol. 63:441444.
87. Percy, N.,, G. J. Belsham,, J. K. Brangwyn,, M. Sullivan,, D. M. Stone,, and J. W. Almond. 1992. Intracellular modifications induced by poliovirus reduce the requirement for structural motifs in the 5' noncoding region of the genome involved in internal initiation of protein synthesis. J. Virol. 66:16951701.
88. Perez, L.,, and L. Carrasco. 1992. Lack of direct correlation between p220 cleavage and the shut-off of host translation after poliovirus infection. Virology 189:178186.
89. Pestova, T. V.,, C. U. T. Hellen,, and E. Wimmer. 1991. Translation of poliovirus RNA: role of an essential cis-acting oligopyrimidine element within the 5' nontranslated region and involvement of a cellular 57-kilodalton protein. J. Virol. 65:61946204.
90. Pilipenko, E. V.,, V. M. Blinov,, L. I. Romanova,, A. N. Sinyakov,, S. V. Maslova,, and V. I. Agol. 1989. Conserved structural domains in the 5' untranslated region of picornaviral genomes: an analysis of the segment controlling translation and neurovirulence. Virology 168:201209.
91. Pilipenko, E.V.,, A. P. Gmyl,, S.V. Maslova,, Y. V. Svitkin,, A. N. Sinyakov,, and V. I. Agol. 1992. Prokaryotic-like cis-elements in the cap-independent internal initiation of translation on picornavirus RNA. Cell 68:119131.
92. Racaniello, V. R.,, and D. Baltimore. 1981. Molecular cloning of poliovirus cDNA and determination of the complete nucleotide sequence of the viral genome. Proc. Natl. Acad. Sci. USA 78:48874891.
93. Racaniello, V. R.,, and C. Meriam. 1986. Poliovirus temperature-sensitive mutant containing a single nucleotide deletion in the 5'-noncoding region of the viral RNA. Virology 155:498507.
94. Rivera, V. M.,, J. D. Welsh,, and J.V. Maizel. 1988. Comparative sequence analysis of the 5' noncoding region of the enteroviruses and rhi-noviruses. Virology 165:4250.
95. Roehl, H. H.,, and B. L. Semler. 1994. In vitro biochemical methods for investigating RNA-protein interactions in picornaviruses. Methods Mol. Genet. 4:160182.
96. Rothberg, P. G.,, T. J. R. Harris,, A. Nomoto,, and E. Wimmer. 1978. O4-(5'-uridylyl)tyrosine is the bond between the genome-linked protein and the RNA of poliovirus. Proc. Natl. Acad. Sci. USA 75:48684872.
97. Rozen, F.,, I. Edery,, K. Meerovitch,, T. E. Dever,, W. C. Merrick,, and N. Sonenberg. 1990. Bidirectional RNA helicase activity of eukaryotic translation initiation factors 4A and 4F. Mol. Cell. Biol. 10:11341144.
98. Rubinstein, S. J.,, and A. Dasgupta. 1989. Inhibition of rRNA synthesis by poliovirus: specific inactivation of transcription factors. J. Virol. 63:46894696.
99. Sarnow, P.,, H. S. Bernstein,, and D. Baltimore. 1986. A poliovirus temperature-sensitive mutant located in a non-coding region of the genome. Proc. Natl. Acad. Sci. USA 83:571575.
100. Simoes, E. A. F.,, and P. Sarnow. 1991. An RNA hairpin at the extreme 5' end of the poliovirus RNA genome modulates viral translation in human cells. J. Virol. 65:913921.
101. 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. 207:379392.
102. Sonenberg, N.,, and K. Meerovitch. 1990. Translation of poliovirus mRNA. Enzyme 44:278291.
103. Stone, D. M.,, J. W. Almond,, J. K. Brangwyn,, and G.J. Belsham. 1993. trans complementation of cap-independent translation directed by poliovirus 5' noncoding region deletion mutants: evidence for RNA-RNA interactions. J. Virol. 67:62156223.
104. Strebel, K.,, and E. Beck. 1986. A second protease of foot-and-mouth disease virus. J. Virol. 58:893899.
105. Toyoda, H.,, M. Kohara,, Y. Kataoka,, T. Suganuma,, T. Omata,, N. Imura,, and A. Nomoto. 1984. Complete nucleotide sequences of all three poliovirus serotype genomes: implication for genetic relationship, gene function, and antigenic determinants. J. Mol. Biol. 174:561585.
106. Trono, D.,, R. Andino,, and D. Baltimore. 1988. An RNA sequence of hundreds of nucleotides at the 5' end of poliovirus RNA is involved in allowing viral protein synthesis. J. Virol. 62:22912299.
107. Witherell, G. W.,, A. Gil,, and E. Wimmer. 1993. Interaction of polypyrimidine tract binding protein with the encephalomyocarditis virus mRNA internal ribosome entry site. Biochemistry 32:82688275.
108. Wyckoff, E. E.,, J. W. B. Hershey,, and E. Ehrenfeld. 1990. Eukaryotic initiation factor 3 is required for poliovirus 2A protease-in-duced cleavage of the p220 component of eukaryotic initiation factor 4E Proc. Natl. Acad. Sci. USA 87:95299533.
109. Wyckoff, E. E.,, R. E. Lloyd,, and E. Ehrenfeld. 1992. Relationship of eukaryotic initiation factor 3 to poliovirus-induced p220 cleavage activity. J. Virol. 66:29432951.
110. Yan, R.,, W. Rychlik,, D. Etchison,, and R. E. Rhoads. 1992. Amino acid sequence of the human protein synthesis initiation factor elF-4 gamma. J. Biol. Chem. 267:2322623231.

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