Processing Determinants and Functions of Cleavage Products of Picornavirus Polyproteins

Louis E.-C. Leong; Christopher T. Cornell; Bert L. Semler

doi:10.1128/9781555817916.ch16

Chapter 16 : Processing Determinants and Functions of Cleavage Products of Picornavirus Polyproteins

Authors: Louis E.-C. Leong¹, Christopher T. Cornell², Bert L. Semler²

VIEW AFFILIATIONS HIDE AFFILIATIONS

Affiliations: 1: Invitrogen Corp., 1600 Faraday Ave., Carlsbad, CA 92008; 2: Department of Microbiology and Molecular Genetics, College of Medicine, University of California, Irvine, CA 92697-4025

Content Type: Monograph

Publication Year: 2002

Category: Viruses and Viral Pathogenesis

Book DOI: 10.1128/9781555817916

Chapter DOI: 10.1128/9781555817916.ch16

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

Preview this chapter:

Processing Determinants and Functions of Cleavage Products of Picornavirus Polyproteins, Page 1 of 2

< Previous page | Next page > /docserver/preview/fulltext/10.1128/9781555817916/9781555812102_Chap16-1.gif /docserver/preview/fulltext/10.1128/9781555817916/9781555812102_Chap16-2.gif

Abstract:

Picornaviruses employ a number of unique intracellular mechanisms and novel processes during their infectious cycles resulting in their being among the most successful of viral pathogens. This chapter begins with a discussion of the features of viral proteinases, continues with an outline of the functions of both precursor and mature viral polypeptides present during a picornaviral infection, and concludes with a brief summary of nonviral substrates cleaved by viral proteinases. Viral proteinases including L protein, 2A proteinase and 3C proteinase have been discussed in the chapter. The aphthoviruses and cardioviruses code for an L protein at the N terminus of their polyproteins. The cleavage activity of the L proteinase from foot-and-mouth disease virus (FMDV), an aphthovirus, has been well characterized. The 3C proteinase activity carries out the majority of the proteolytic processing of the viral polyprotein. The evolution of picornaviruses might dictate that the P1 to PN substrate positions be identical or similar to optimize polyprotein processing and maximize the generation of mature viral proteins. In vitro synthesized viral RNAs containing large inframe deletions within the P1 region are self-replicating in cultured cells, suggesting that the proteins required for viral RNA replication are located primarily within the P2 and P3 (nonstructural) regions of the genome. Since picornaviruses utilize a mechanism of translation that is cap independent, it is advantageous to the virus to inhibit nonessential cap-dependent cellular translation.

Citation: Leong L, Cornell C, Semler B. 2002. Processing Determinants and Functions of Cleavage Products of Picornavirus Polyproteins, p 187-197. In Semler B, Wimmer E (ed), Molecular Biology of Picornavirus. ASM Press, Washington, DC. doi: 10.1128/9781555817916.ch16

Key Concept Ranking

Theiler's Murine Encephalomyelitis: 0.42602193

0.42602193

Highlighted Text: Show | Hide

Full text loading...

Figures

Processing Determinants and Functions of Cleavage Products of Picornavirus Polyproteins

[com.pub2web.rdf.cci.facet.ContentItem[id=http://asm.metastore.ingenta.com/content/author/10.1128/9781555817916.chap16-1,webId=/content/author/10.1128/9781555817916.chap16-1,properties={foaf_givenname=Louis E.-C., foaf_name=Louis E.-C. Leong, foaf_surname=Leong, pub_isAffiliatedWith=[com.pub2web.rdf.cci.facet.ContentItem[id=http://asm.metastore.ingenta.com/content/affiliation/10.1128/9781555817916.chap16-aff1]]}], com.pub2web.rdf.cci.facet.ContentItem[id=http://asm.metastore.ingenta.com/content/author/10.1128/9781555817916.chap16-2,webId=/content/author/10.1128/9781555817916.chap16-2,properties={foaf_givenname=Christopher T., foaf_name=Christopher T. Cornell, foaf_surname=Cornell, pub_isAffiliatedWith=[com.pub2web.rdf.cci.facet.ContentItem[id=http://asm.metastore.ingenta.com/content/affiliation/10.1128/9781555817916.chap16-aff2]]}], com.pub2web.rdf.cci.facet.ContentItem[id=http://asm.metastore.ingenta.com/content/author/10.1128/9781555817916.chap16-3,webId=/content/author/10.1128/9781555817916.chap16-3,properties={foaf_givenname=Bert L., foaf_name=Bert L. Semler, foaf_surname=Semler, pub_isAffiliatedWith=[com.pub2web.rdf.cci.facet.ContentItem[id=http://asm.metastore.ingenta.com/content/affiliation/10.1128/9781555817916.chap16-aff2]]}]]

/content/10.1128/9781555817916.chap16.fig16-1

FIGURE 1

Map of proteins encoded in picornavirus genomes. Shown is a schematic of a typical picornaviral genome. The 5′ end is covalently linked to the viral protein VPg (protein 3B), and the poly(A) tail at the 3′ end is genetically coded. The polyprotein is divided into structural (P1) and nonstructural products (P2 and P3). The vertical lines represent sites along the polyprotein that are cleaved by viral proteinases; however, there are precursor proteins (e.g., 2BC, 3AB, 3CD) that have functions distinct from their mature cleavage products. Only cardioviruses and aphthoviruses encode an L protein. The viral proteinase responsible for the majority of polyprotein processing is the 3C chymotrypsin-like proteinase, and precursor polypeptides contain 3C sequences (e.g., 3CD). In addition, enteroviruses and rhinoviruses utilize the 2A proteinase to carry out the primary cleavage event between the carboxy terminus of the P1 region and the amino terminus of 2A. Cardioviruses and aphthoviruses do not contain a proteolytically active form of 2A; however, this protein is self-cleaved from the amino terminus of 2B by an undefined mechanism. The L proteinase of aphthoviruses is a cysteine-type proteinase that cleaves between its carboxy terminus and the amino terminus of VP4. The L proteinase of cardioviruses is cleaved from the polyprotein at its amino terminus by 3C. Interestingly, aphthoviruses are unique in that they encode three tandemly repeated VPgs while all other picornavirus genomes contain only one VPg.

10.1128/9781555817916/fig16-1_thmb.gif

10.1128/9781555817916/fig16-1.gif

FIGURE 1

/content/10.1128/9781555817916.chap16.fig16-2

FIGURE 2

Processing of P1 capsid proteins and assembly of virion particles. 3CD carries out the cleavage of the P1 capsid precursor in a reaction that requires the activity of a cellular cofactor. This results in the formation of VP0, VP3, and VP1, which assemble into a 5S protomer. Then, five protomers assemble to form the 14S protomer. Twelve 14S protomers then either assemble around an RNA molecule or form the 80S procapsid structure into which an RNA molecule is threaded. In either case, this assembly process results in the formation of a short-lived 150S provirion. Finally, this newly formed particle undergoes a maturation event (occurring by an undefined mechanism) resulting in the cleavage of VP0 into VP2 and VP4, resulting in the production of a mature virion.

10.1128/9781555817916/fig16-2_thmb.gif

10.1128/9781555817916/fig16-2.gif

FIGURE 2

References

/content/book/10.1128/9781555817916.chap16

1. Aldabe, R.,, A. Barco,, and L. Carrasco. 1996. Membrane permeabilization by poliovirus proteins 2B and 2BC. J. Biol. Chem. 271: 23134– 23137.

2. Aldabe, R.,, and L. Carrasco. 1995. Induction of membrane proliferation by poliovirus proteins 2C and 2BC. Biochem. Biophys. Res. Commun. 206: 64– 76.

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. Ansardi, D. C.,, R. Pal-Ghosh,, D. Porter,, and C. D. Morrow. 1995. Encapsidation and serial passage of a poliovirus replicon which expresses an inactive 2A proteinase. J. Virol. 69: 1359– 1366.

7. Arnold, E.,, M. Luo,, G. Vriend,, M. G. Rossmann,, A. C. Palmenberg,, G. D. Parks,, M. J. Nicklin,, and E. Wim-mer. 1987. Implications of the picornavirus capsid structure for polyprotein processing. Proc. Natl. Acad. Sci. USA 84: 21– 25.

8. Banerjee, R.,, A. Echeverri,, and A. Dasgupta. 1997. Poliovirus-encoded 2C polypeptide specifically binds to the 3'-terminal sequences of viral negative-strand RNA. J. Virol. 71: 9570– 9578.

9. Banerjee, R.,, W. Tsai,, W. Kim,, and A. Dasgupta. 2001. Interaction of poliovirus-encoded 2C/2BC polypeptides with the 3' terminus negative-strand cloverleaf requires an intact stem-loop B. Virology 280: 41– 51.

10. Barco, A.,, and L. Carrasco. 1998. Identification of regions of poliovirus 2BC protein that are involved in cytotoxicity. J. Virol. 72: 3560– 3570.

11. Barton, D. J.,, and J. B. Flanegan. 1997. Synchronous replication of poliovirus RNA: initiation of negative-strand RNA synthesis requires the guanidine-inhibited activity of protein 2C. J. Virol. 71: 8482– 8489.

12. Bazan, J. E.,, 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.

13. 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.

14. Bienz, K.,, D. Egger,, and L. Pasamontes. 1987. Association of polioviral proteins of the P2 genomic region with the viral replication complex and virus-induced membrane synthesis as visualized by electron microscopic immunocytochemistry and autoradiography. Virology 160: 220– 226.

15. Bienz, K.,, D. Egger,, Y. Rasser,, and W. Bossart. 1983. Intracellular distribution of poliovirus proteins and the induction of virus-specific cytoplasmic structures. Virology 131: 39– 48.

16. Blair, W. S.,, X. Li,, and B. L. Semler. 1993. A cellular cofactor facilitates efficient 3CD cleavage of the poliovirus P1 precursor.;. Virol. 67: 2336– 2343.

17. Blair, W. S.,, T. B. Parsley,, H. P. Bogerd,, J. S. Towner,, B. L. Semler,, and B. R. Cullen. 1998. Utilization of a mammalian cell-based RNA binding assay to characterize the RNA binding properties of picornavirus 3C proteinases. RNA 4: 215– 225.

18. Blair, W. S.,, and B. L. Semler. 1991. Role for the P4 amino acid residue in substrate utilization by the poliovirus 3CD proteinase. J. Virol. 65: 6111– 6123.

19. Bolten, R.,, D. Egger,, R. Gosert,, G. Schaub,, L. Landmann,, and K. Bienz. 1998. Intracellular localization of poliovirus. J. Virol. 72: 8578– 8585.

20. Charini, W. A.,, S. Todd,, G. A. Gutman,, and B. L. Semler. 1994. Transduction of a human RNA sequence by poliovirus. J. Virol. 68: 6547– 6552.

21. 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.

22. Chen, H. H.,, W. P. Kong,, and R. P. Roos. 1995. The leader peptide of Theiler's murine encephalomyelitis virus is a zinc-binding protein. J. Virol. 69: 8076– 8078.

23. Chen, H. H.,, W. P. Kong,, L. Zhang,, P. L. Ward,, and R. P. Roos. 1995. A picornaviral protein synthesized out of frame with the polyprotein plays a key role in a virus-induced immune-mediated demyelinating disease. Nat. Med. 1: 927– 931.

24. Cho, M. W.,, N. Teterina,, D. Egger,, K. Bienz,, and E. Ehrenfeld. 1994. Membrane rearrangement and vesicle induction by recombinant poliovirus 2C and 2BC in human cells. Virology 202: 129– 145.

25. 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: 1232– 1237.

26. 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: 6480– 6488.

27. Cordingley, M. G.,, P. L. Callahan,, V. V. Sardana,, V. M. Garsky,, and R. J. Colonno. 1990. Substrate requirements of human rhinovirus 3C protease for peptide cleavage in vitro. J. BioL Chem. 265: 9062– 9065.

28. Cui, T.,, and A. G. Porter. 1995. Localization of binding site for encephalomyocarditis virus RNA polymerase in the 3'-noncoding region of the viral RNA. Nucleic Acids Res. 23: 377– 382.

29. Cui, T.,, S. Sankar,, and A. G. Porter. 1993. Binding of encephalomyocarditis virus RNA polymerase to the 3'-noncoding region of the viral RNA is specific and requires the 3'-poly(A) tail. J. Biol. Chem. 268: 26093– 26098.

30. Das, S.,, and A. Dasgupta. 1993. Identification of the cleavage site and determinants required for poliovirus 3C pro-catalyzed cleavage of human TATA-binding transcription factor TBP. J. Virol. 67: 3326– 3331.

31. Datta, U.,, and A. Dasgupta. 1994. Expression and subcellular localization of poliovirus VPg-precursor protein 3AB in eukaryotic cells: evidence for glycosylation in vitro. J. Virol. 68: 4468– 4477.

32. Deitz, S. B.,, D. A. Dodd,, S. Cooper,, P. Parham,, and K. Kirkegaard. 2000. MHC I-dependent antigen presentation is inhibited by poliovirus protein 3A. Proc. Natl. Acad. Sci. USA 97: 13790– 13795.

33. 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: 4407– 4409.

34. 34- 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.

35. Dewalt, P. G.,, and B. L. Semler. 1987. Site-directed mutagenesis of proteinase 3C results in a poliovirus deficient in synthesis of viral RNA polymerase. J. Virol. 61: 2162– 2170.

36. Doedens, J. R.,, T. H. Giddings,, and K. Kirkegaard. 1997. Inhibition of endoplasmic reticulum-to-Golgi traffic by poliovirus protein 3A: genetic and ultrastructural analysis. J. Virol. 71: 9054– 9064.

37. Doedens, J. R.,, and K. Kirkegaard. 1995. Inhibition of cellular protein secretion by poliovirus proteins 2B and 3A. EMBO J. 14: 894– 907.

38. Etchison, D.,, S. C. Milburn,, I. Edery,, N. Sonenberg,, and J. W. 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: 14806– 14810.

39. Flanegan, J. B.,, R. F. Pettersson,, V. Ambros,, N. J. Hewlett,, and D. Baltimore. 1977. Covalent linkage of a protein to a defined nucleotide sequence at the 5'-terminus of virion and replicative intermediate RNAs of poliovirus. Proc. Natl. Acad. Sci. USA 74: 961– 965.

40. Goodfellow, I.,, Y. Chaudhry,, A. Richardson,, J. Meredith,, J. W. Almond,, W. Barclay,, and D. J. Evans. 2000. Identification of a cis-acting replication element within the poliovirus coding region. J. Virol. 74: 4590– 4600.

41. 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.

42. Gorbalenya, A. E.,, V. M. Blinov,, A. P. Donchenko,, and E. V. Koonin. 1989. An NTP-binding motif is the most conserved sequence in a highly diverged monophyletic group of proteins involved in positive strand RNA viral replication. J. Mol. Evol. 28: 256– 268.

43. 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..

44. Gorbalenya, A. E.,, and E. V. Koonin. 1989. Viral proteins containing the purine NTP-binding sequence pattern. Nucleic Acids Res. 17: 8413– 8440.

45. Gorbalenya, A. E.,, E. V. Koonin,, A. P. Donchenko,, and V. M. Blinov. 1988. A conserved NTP-motif in putative helicases. Nature 333: 22.

46. 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.

47. Gradi, A.,, Y. V. Svitkin,, H. Imataka,, and N. Sonenberg. 1998. Proteolysis of human eukaryotic translation initiation factor eIF4GII, but not eIF4GI, coincides with the shutoff of host protein synthesis after poliovirus infection. Proc. Natl. Acad. Sci. USA 95: 11089– 11094.

48. Grubman, M. J.,, and B. Baxt. 1982. Translation of foot-and-mouth disease virion RNA and processing of the primary cleavage products in a rabbit reticulocyte lysate. Virology 116: 19– 30.

49. 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.

50. Haller, A. H.,, and B. L. Semler,. 1995. Translation and host cell shut off, p. 113– 133. In H. A. Rotbart (ed.), Human Enterovirus Infections. ASM Press, Washington, D.C..

51. 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.

52. Harris, K. S.,, S. R. Reddigari,, M. J. Nicklin,, T. Ham-merle,, and E. Wimmer. 1992. Purification and characterization of poliovirus polypeptide 3CD, a proteinase and a precursor for RNA polymerase. J. Virol. 66: 7481– 7489.

53. Harris, K. S.,, W. Xiang,, L. Alexander,, W. S. Lane,, A. V. Paul,, and E. Wimmer. 1994 - Interaction of poliovirus polypeptide 3CD pro 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.

54. Hellen, C. U.,, C. K. Lee,, and E. Wimmer. 1992. Determinants of substrate recognition by poliovirus 2A proteinase. J. Virol. 66: 3330– 3338.

55. Herold, J.,, and R. Andino. 2001. Poliovirus RNA replication requires genome circularization through a protein-protein bridge. Mol. Cell 7: 581– 591.

56. Hope, D. A.,, S. E. Diamond,, and K. Kirkegaard. 1997. Genetic dissection of interaction between poliovirus 3D polymerase and viral protein 3AB. J. Virol. 71: 9490– 9498.

57. Ivanoff, L. A.,, T. Towatari,, J. Ray,, B. D. Korant,, and S. R. Petteway, Jr. 1986. Expression and site-specific mutagenesis of the poliovirus 3C protease in Escherichia coli. Proc. Natl. Acad. Sci. USA 83: 5392– 5396.

58. Jang, S. K.,, H. G. Krausslich,, M. J. Nicklin,, G. M. Duke,, A. C. Palmenberg,, and E. Wimmer. 1988. A segment of the 5' nontranslated region of encephalomyocarditis virus RNA directs internal entry of ribosomes during in vitro translation. J. Virol. 62: 2636– 2643.

59. Joachims, M.,, P. C. Van Breugel,, and R. E. Lloyd. 1999. Cleavage of poly(A)-binding protein by enterovirus proteases concurrent with inhibition of translation in vitro. J. Virol. 73: 718– 727.

60. 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: 4341– 4349.

61. Kaplan, G.,, and V. R. Racaniello. 1988. Construction and characterization of poliovirus subgenomic replicons. J. Virol. 62: 1687– 1696.

62. Kean, K. M.,, N. Teterina,, and M. Girard. 1990. Cleavage specificity of the poliovirus 3C protease is not restricted to Gln-Gly at the 3C/3D junction. J. Gen. Virol. 71( Pt. ll): 2553– 2563.

63. 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.

64. Kerekatte, V.,, B. D. Keiper,, C. Badorff,, A. Cai,, K. U. Knowlton,, and R. E. Rhoads. 1999. Cleavage of poly(A)-binding protein by coxsackievirus 2A protease in vitro and in vivo: another mechanism for host protein synthesis shutoff? J. Virol. 73: 709– 717.

65. Kirchweger, R.,, E. Ziegler,, B. J. Lamphear,, D. Waters,, H. D. Liebig,, W. Sommergruber,, F. Sobrino,, C. Hohenadl,, D. Blaas,, and R. E. Rhoads. 1994. Foot-and-mouth disease virus leader proteinase: purification of the Lb form and determination of its cleavage site on eIF-4 gamma. J. Virol. 68: 5677– 5684.

66. 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 291: 547– 553.

67. Klein, M.,, H. J. Eggers,, and B. Nelsen-Salz. 1999. Echo-virus 9 strain barty non-structural protein 2C has NTPase activity. Virus Res. 65: 155– 160.

68. Kleina, L. G.,, and M. J. Grubman. 1992. Antiviral effects of a thiol protease inhibitor on foot-and-mouth disease virus. J. Virol. 66: 7168– 7175.

69. Kong, J. S.,, S. Venkatraman,, K. Furness,, S. Nimkar,, T. A. Shepherd,, Q. M. Wang,, J. Aube,, and R. P. Hanzlik. 1998. Synthesis and evaluation of peptidyl Michael acceptors that inactivate human rhinovirus 3C protease and inhibit virus replication. J. Med. Chem. 41: 2579– 2587.

70. Krausslich, H. G.,, M. J. Nicklin,, H. Toyoda,, D. Etchison,, and E. Wimmer. 1987. Poliovirus proteinase 2A induces cleavage of eucaryotic initiation factor 4F polypeptide p220. J. Virol. 61: 2711– 2718.

71. Kusov, Y.,, and V. Gauss-Muller. 1999. Improving proteolytic cleavage at the 3A/3B site of the hepatitis A virus polyprotein impairs processing and particle formation, and the impairment can be complemented in trans by 3AB and 3ABC. J. Virol. 73: 9867– 9878.

72. Lama, J.,, and L. Carrasco. 1992. Expression of poliovirus nonstructural proteins in Escherichia coli cells. Modification of membrane permeability induced by 2B and 3A. J. Biol. Chem. 267: 15932– 15937.

73. 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.

74. Lawson, M. A.,, and B. L. Semler. 1991. Poliovirus thiol proteinase 3C can utilize a serine nucleophile within the putative catalytic triad. Proc. Natl. Acad. Sci. USA 88: 9919– 9923.

75. Lee, Y. E.,, A. Nomoto,, B. M. Detjen,, and E. Wimmer. 1977. A protein covalently linked to poliovirus genome RNA. Proc. Natl. Acad. Sci. USA 74: 59– 63.

76. 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.

77. Li, X.,, H. H. Lu,, S. Mueller,, and E. Wimmer. 2001. The C-terminal residues of poliovirus proteinase 2A(pro) are critical for viral RNA replication but not for cis- or trans-proteolytic cleavage. J. Gen. Virol. 82: 397– 408.

78. Lobert, P. E.,, N. Escriou,, J. Ruelle,, and T. Michiels. 1999. A coding RNA sequence acts as a replication signal in cardioviruses. Proc. Natl. Acad. Sci. USA 96: 11560– 11565.

79. Long, A. C.,, D. C. Orr,, J. M. Cameron,, B. M. Dunn,, and J. Kay. 1989. A consensus sequence for substrate hydrolysis by rhinovirus 3C proteinase. FEBS Lett. 258: 75– 78.

80. Macejak, D. G.,, and P. Sarnow. 1992. Association of heat shock protein 70 with enterovirus capsid precursor P1 in infected human cells. J. Virol. 66: 1520– 1527.

81. Matthews, D. A.,, W. W. Smith,, R. A. Ferre,, B. Condon,, G. Budahazi,, W. Sisson,, J. E. Villafranca,, C. A. Janson,, H. E. McElroy,, and C. L. Gribskov. 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.

82. McKnight, K. L.,, and S. M. Lemon. 1998. The rhinovirus type 14 genome contains an internally located RNA structure that is required for viral replication. RNA 4: 1569– 1584.

83. Mirzayan, C.,, and E. Wimmer. 1992. Genetic analysis of an NTP-binding motif in poliovirus polypeptide 2C. Virology 189: 547– 555.

84. Mirzayan, C.,, and E. Wimmer. 1994. Biochemical studies on poliovirus polypeptide 2C: evidence for ATPase activity. Virology 199: 176– 187.

85. Molla, A.,, A. V. Paul,, and E. Wimmer. 1991. Cell-free, de novo synthesis of poliovirus. Science 254: 1647– 1651.

86. 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.

87. Nomoto, A.,, B. Detjen,, R. Pozzatti,, and E. Wimmer. 1977. The location of the polio genome protein in viral RNAs and its implication for RNA synthesis. Nature 268: 208– 213.

88. Nomoto, A.,, N. Kitamura,, F. Golini,, and E. Wimmer. 1977. The 5'-terminal structures of poliovirion RNA and poliovirus mRNA differ only in the genome-linked protein VPg. Proc. Natl. Acad. Sci. USA 74: 5345– 5349.

89. Ohlmann, T.,, M. Rau,, V. M. Pain,, and S. J. Morley. 1996. The C-terminal domain of eukaryotic protein synthesis initiation factor (eIF) 4G is sufficient to support cap-independent translation in the absence of eIF4E. EMBO J. 15: 1371– 1382.

90. Pal-Ghosh, R.,, and C. D. Morrow. 1993. A poliovirus minireplicon containing an inactive 2A proteinase is expressed in vaccinia virus-infected cells. J. Virol. 67: 4621– 4629.

91. Pallai, P. V.,, F. Burkhardt,, M. Skoog,, K. Schreiner,, P. Bax,, K. A. Cohen,, G. Hansen,, D. E. Palladino,, K. S. Harris,, and M. J. Nicklin. 1989. Cleavage of synthetic peptides by purified poliovirus 3C proteinase. J. Biol. Chem. 264: 9738– 9741.

92. 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.

93. Palmenberg, A. C. 1990. Proteolytic processing of picornaviral polyprotein. Annu. Rev. Microbiol. 44: 603– 623.

94. 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: 376– 384.

95. Parsley, T. B.,, C. T. Cornell,, and B. L. Semler. 1999. Modulation of the RNA binding and protein processing activities of poliovirus polypeptide 3CD by the viral RNA polymerase domain. J. Biol. Chem. 274: 12867– 12876.

96. 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: 1124– 1134.

97. Paul, A. V.,, J. H. van Boom,, D. Filippov,, and E. Wimmer. 1998. Protein-primed RNA synthesis by purified poliovirus RNA polymerase. Nature 393: 280– 284.

98.. 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.

99. 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.

100. Petithory, J.R.,, F. R. Masiarz,, J. F. Kirsch,, D. V. Santi,, and B. A. Malcolm. 1991. A rapid method for determination of endoproteinase substrate specificity: specificity of the 3C proteinase from hepatitis A virus. Proc. Natl. Acad. Sci. USA 88: 11510– 11514.

101. Pettersson, R. F.,, V. Ambros,, and D. Baltimore. 1978. Identification of a protein linked to nascent poliovirus RNA and to the polyuridylic acid of negative-strand RNA. J. Virol. 27: 357– 365.

102. Pfister, T.,, and E. Wimmer. 1999. Characterization of the nucleoside triphosphatase activity of poliovirus protein 2C reveals a mechanism by which guanidine inhibits poliovirus replication. J. Biol. Chem. 274: 6992– 7001.

103. Piccone, M. E.,, M. Zellner,, T. F. Kumosinski,, P. W. Mason,, and M. J. Grubman. 1995. Identification of the active-site residues of the L proteinase of foot-and-mouth disease virus. J. Virol. 69: 4950– 4956.

104. Pincus, S. E.,, D. C. Diamond,, E. A. Emini,, and E. Wimmer. 1986. Guanidine-selected mutants of poliovirus: mapping of point mutations to polypeptide 2C. J. Virol. 57: 638– 646.

105. Racaniello, V. R.,, and D. Baltimore. 1981. Cloned poliovirus complementary DNA is infectious in mammalian cells. Science 214: 916– 919.

106. Richards, O. C.,, and E. Ehrenfeld. 1998. Effects of poliovirus 3AB protein on 3D polymerase-catalyzed reaction. J. Biol. Chem. 273: 12832– 12840.

107. Rieder, E.,, A. V. Paul,, D. W. Kim,, J. H. van Boom,, and E. Wimmer. 2000. Genetic and biochemical studies of poliovirus cis-acting replication element cre in relation to VPg uridylylation. J. Virol. 74: 10371– 10380.

108. Rodriguez, P. L.,, and L. Carrasco. 1995. Poliovirus protein 2C contains two regions involved in RNA binding activity. J. Biol. Chem. 270: 10105– 10112.

109. Rueckert, R. R.,, and E. Wimmer. 1984. Systematic nomenclature of picornavirus proteins. J. Virol. 50: 957– 959.

110. 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.

111. Sandoval, I. V.,, and L. Carrasco. 1997. Poliovirus infection and expression of the poliovirus protein 2B provoke the disassembly of the Golgi complex, the organelle target for the antipoliovirus drug Ro-090179. J. Virol. 71: 4679– 4693.

112. Schechter, I.,, and A. Berger. 1967. On the size of the active site in proteases. I. Papain. Biochem. Biophys. Res. Commun. 27: 157– 162.

113. Semler, B. L.,, C. W. Anderson,, R. Hanecak,, L. F. Dorner,, and E. Wimmer. 1982. A membrane-associated precursor to poliovirus VPg identified by immunoprecipitation with antibodies directed against a synthetic heptapeptide. Cell 28: 405– 412.

114. Semler, B. L.,, A. J. Dorner,, and E. Wimmer. 1984. Production of infectious poliovirus from cloned cDNA is dramatically increased by SV40 transcription and replication signals. Nucleic Acids Res. 12: 5123– 5141.

115. Sommergruber, W.,, H. Ahorn,, H. Klump,, J. Seipelt,, A. Zoephel,, F. Fessl,, E. Krystek,, D. Blaas,, E. Kuechler,, H. D. Liebig, et al. 1994 - 2A proteinases of coxsackie-and rhinovirus cleave peptides derived from eIF-4G via a common recognition motif. Virology 198: 741– 745.

116. Strebel, K.,, and E. Beck. 1986. A second protease of foot-and-mouth disease virus. J. Virol. 58: 893– 899.

117. Suhy, D. A.,, T. H. Giddings, Jr.,, and K. Kirkegaard. 2000. Remodeling the endoplasmic reticulum by poliovirus infection and by individual viral proteins: an autophagy-like origin for virus-induced vesicles. J. Virol. 74: 8953– 8965.

118. Summers, D. F.,, and J. V. J. Maizel. 1968. Evidence for large precursor proteins in poliovirus synthesis. Proc. Natl. Acad. Sci. USA 59: 966– 971.

119. Svitkin, Y. V.,, A. Gradi,, H. Imataka,, S. Morino,, and N. Sonenberg. 1999. Eukaryotic initiation factor 4GII (eIF4GII), but not eIF4GI, cleavage correlates with inhibition of host cell protein synthesis after human rhinovirus infection. J. Virol. 73: 3467– 3472.

120. Takata, H.,, M. Obuchi,, J. Yamamoto,, T. Odagiri,, R. P. Roos,, H. Iizuka,, and Y. Ohara. 1998. L* protein of the DA strain of Theiler's murine encephalomyelitis virus is important for virus growth in a murine macrophage-like cell line. J. Virol. 72: 4950– 4955.

121. Teterina, N. L.,, K. Bienz,, D. Egger,, A. E. Gorbalenya,, and E. Ehrenfeld. 1997. Induction of intracellular membrane rearrangements by HAV proteins 2C and 2BC. Virology 237: 66– 77.

122. Towner, J. S.,, T. V. Ho,, and B. L. Semler. 1996. Determinants of membrane association for poliovirus protein 3AB. J. Biol. Chem. 271: 26810– 26818.

123. van der Werf, S.,, J. Bradley,, E. Wimmer,, F. W. Studier,, and J. J. Dunn. 1986. Synthesis of infectious poliovirus RNA by purified T7 RNA polymerase. Proc. Natl. Acad. Sci. USA 83: 2330– 2334.

124. van Kuppeveld, F. J.,, J. M. Galama,, J. Zoll,, and W. J. Melchers. 1995. Genetic analysis of a hydrophobic domain of coxsackie B3 virus protein 2B: a moderate degree of hydrophobicity is required for a cis-acting function in viral RNA synthesis. J. Virol. 69: 7782– 7790.

125. van Kuppeveld, F. J.,, J. G. Hoenderop,, R. L. Smeets,, P. H. Willems,, H. B. Dijkman,, J. M. Galama,, and W. J. Melchers. 1997. Coxsackievirus protein 2B modifies endoplasmic reticulum membrane and plasma membrane permeability and facilitates virus release. EMBO J. 16: 3519– 3532.

126. van Kuppeveld, F. J.,, W. J. Melchers,, K. Kirkegaard,, and J. R. Doedens. 1997. Structure-function analysis of coxsackie B3 virus protein 2B. Virology 227: 111– 118.

127. Wells, S. E.,, P. E. Hillner,, R. D. Vale,, and A. B. Sachs. 1998. Circularization of mRNA by eukaryotic translation initiation factors. Mol. Cell 2: 135– 140.

128. Wimmer, E.,, C. U. Hellen,, and X. Cao. 1993. Genetics of poliovirus. Annu. Rev. Genet. 27: 353– 436.

129. 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: 6732– 6741.

130. 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: 892– 904.

131. Yalamanchili, P.,, R. Banerjee,, and A. Dasgupta. 1997. Poliovirus-encoded protease 2A pro cleaves the TATA-binding protein but does not inhibit host cell RNA polymerase II transcription in vitro. J. Virol. 71: 6881– 6886.

132. Yalamanchili, P.,, U. Datta,, and A. Dasgupta. 1997. Inhibition of host cell transcription by poliovirus: cleavage of transcription factor CREB by poiiovirus-encoded protease 3C pro. J. Virol. 71: 1220– 1226.

133. Yalamanchili, P.,, K. Weidman,, and A. Dasgupta. 1997. Cleavage of transcriptional activator Oct-1 by poliovirus encoded protease 3C pro. Virology 239: 176– 185.

134. Ypma-Wong, M. E, 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.

135. Yu, S. E, and R. E. Lloyd. 1991. Identification of essential amino acid residues in the functional activity of poliovirus 2A protease. Virology 182: 615– 625.

Tables

Processing Determinants and Functions of Cleavage Products of Picornavirus Polyproteins

/content/10.1128/9781555817916.chap16.tab16-1

TABLE 1

Functions of picornavirus polypeptides

10.1128/9781555817916/tab16-1_thmb.gif

10.1128/9781555817916/tab16-1.gif

TABLE 1

Functions of picornavirus polypeptides