Nucleocytoplasmic Traffic Disorder Induced by Cardioviruses

Peter Lidsky

Stanleyson Hato

Maryana Bardina

Alexei Aminev

M. P. Chumakov Institute of Poliomyelitis and Viral Encephalitides, Russian Academy of Medical Sciences, Moscow Region 142782, Russia,^{M. V. Lomonosov Moscow State University, Moscow 119899, Russia,}^{Department of Medical Microbiology, Radboud University Nijmegen Medical Centre, Nijmegen Centre for Molecular Life Sciences, Nijmegen 6500 HB, The Netherlands,}^{Institute for Molecular Virology, University of Wisconsin-Madison, Madison, Wisconsin 53706}⁴

^{Corresponding author. Mailing address: Institute of Poliomyelitis and Viral Encephalitides, Russian Academy of Medical Sciences, Moscow Region 142782, Russia. Phone: 7 495 439 9026. Fax: 7 495 439 9321. E-mail:}ur.usm.yksrezoleb@loga.

^{P.V.L., S.H., and M.V.B. contributed equally to this study.}

Received 2005 Aug 13; Accepted 2005 Dec 21.

Abstract

Some picornaviruses, for example, poliovirus, increase bidirectional permeability of the nuclear envelope and suppress active nucleocytoplasmic transport. These activities require the viral protease 2A^{. Here, we studied nucleocytoplasmic traffic in cells infected with encephalomyocarditis virus (EMCV; a cardiovirus), which lacks the poliovirus 2A}^{-related protein. EMCV similarly enhanced bidirectional nucleocytoplasmic traffic. By using the fluorescent “Timer” protein, which contains a nuclear localization signal, we showed that the cytoplasmic accumulation of nuclear proteins in infected cells was largely due to the nuclear efflux of “old” proteins rather than impaired active nuclear import of newly synthesized molecules. The nuclear envelope of digitonin-treated EMCV-infected cells permitted rapid efflux of a nuclear marker protein. Inhibitors of poliovirus 2A}^{did not prevent the EMCV-induced efflux. Extracts from EMCV-infected cells and products of in vitro translation of viral RNAs contained an activity increasing permeability of the nuclear envelope of uninfected cells. This activity depended on the expression of the viral leader protein. Mutations disrupting the zinc finger motif of this protein abolished its efflux-inducing ability. Inactivation of the L protein phosphorylation site (Thr47→Ala) resulted in a delayed efflux, while a phosphorylation-mimicking (Thr47→Asp) replacement did not significantly impair the efflux-inducing ability. Such activity of extracts from EMCV-infected cells was suppressed by the protein kinase inhibitor staurosporine. As evidenced by electron microscopy, cardiovirus infection resulted in alteration of the nuclear pores, but it did not trigger degradation of the nucleoporins known to be degraded in the poliovirus-infected cells. Thus, two groups of picornaviruses, enteroviruses and cardioviruses, similarly alter the nucleocytoplasmic traffic but achieve this by strikingly different mechanisms.}

Abstract

Picornaviruses, small nonenveloped icosahedral animal viruses with a single-stranded RNA genome of positive (mRNA) polarity, encompass the Enterovirus, Rhinoviruses, Cardiovirus, Aphthovirus, Parechovirus, and some other genera (64). All essential steps of their reproduction, such as translation, RNA synthesis, and encapsidation, take place in the cytoplasm of infected cells. The nonessential role of the nucleus for their reproduction follows from their ability to fulfill the complete infectious cycle in nuclei-free cytoplasts (31, 60) or cytoplasmic extracts (7, 52, 71). This fact, however, does not mean that the nuclei are not involved in the infectious process. Indeed, virus-specific proteins have been detected in the nuclei of poliovirus-infected (11, 29) and encephalomyocarditis virus (EMCV)-infected (5, 6) cells. Poliovirus proteases 2A and 3C are known to target a variety of nuclear transcription factors and histones (66, 78, 79, 80). The EMCV 2A protein enters the nucleoli and interacts there with a ribosome precursor, contributing thereby to alterations in the translation control of the virus-infected cells (5, 49). Also, nuclear changes occurring during the apoptotic response to infection with poliovirus (3, 9, 73), coxsackievirus B3 (38), Theiler's murine encephalomyelitis virus (TMEV) (41), and foot-and-mouth disease virus (56) imply that the relevant cytoplasmic host proteins, e.g., caspases and DNases, also find their way into nuclei of the infected cells. On the other hand, picornavirus infection triggers translocation of a number of nuclear host proteins into the cytoplasm where they may stimulate translation (12, 37, 40, 50, 70) and replication (48, 74) of the viral genome. Thus, the macromolecular nucleocytoplasmic exchange plays a significant part in the outcome of the picornavirus infection.

Such exchange, in uninfected cells, is a tightly regulated process. The central role in the nucleocytoplasmic transport is played by a 125-MDa structure called nuclear pore complex (NPC), which forms an aqueous channel in the nuclear envelope. It is composed of about 30 different proteins called nucleoporins (Nup), forming an eightfold symmetrical core, which surrounds the channel and carries filamentous extensions directed to both the cytoplasm and nucleus. Small molecules such as ions, metabolites, and even proteins with a molecular mass below 40 kDa can cross the NPC channel in the nuclear envelope by simple diffusion (25). Generally, the proteins that need to be transported into the nucleus must contain nuclear localization signals (NLS), which are most commonly represented by arginine-lysine-rich motifs (55). These “classical” NLS are recognized in the cytoplasm by their soluble receptor, importin-α/β. The resulting complex docks at a nuclear pore receptor binding site and is transferred into the nucleus, where the cargo dissociates and the receptor is reexported back to the cytoplasm. The directionality of transport is achieved with the aid of a small GTPase Ran, which differently affects the stability of importin-cargo complexes depending on whether it is in a GTP-bound or GDP-bound form (32). The nuclear export machinery works similarly and usually exploits a variety of nuclear export signals and carriers (55). Thus, the NPC, in collaboration with a set of carriers and their regulators, is responsible for the recognition and translocation of specific cargoes in and out of the nucleus, thereby controlling appropriate compartmentation of high-molecular-mass soluble compounds.

Some picornaviruses are known to affect the normal control of nucleocytoplasmic traffic. Two relevant mechanisms have been described. Poliovirus infection induces an increase in the bidirectional permeability of the nuclear envelope, apparently due to the destruction of nuclear pores, as visualized by electron microscopy (8, 10). In addition, active nuclear import via different pathways is also impaired in cells infected with poliovirus and rhinovirus (34, 35). Both these events seem to be caused by the proteolysis of some components on the NPC, such as nucleoporins p62, Nup153, and Nup98 (34), accomplished directly or indirectly by the viral 2A^{protease activity (}10; K. Gustin, T. Skern, N. Park, and M. Halver, Abstr. Meeting of the European Study Group on the Molecular Biology of Picornaviruses, Lunteren, The Netherlands, abstr. G08, 2005).

Although different picornaviruses share many aspects of genome organization, they can differ from one another in important features (Fig. (Fig.1)1) (2). Thus, a protein structurally and functionally similar to the enterovirus and rhinovirus 2A^{is absent from cardioviruses, aphthoviruses, and parechoviruses. In fact, the 2A proteins of these latter three virus groups share with 2A proteins of enteroviruses and rhinoviruses nothing except the name and position in the viral polyprotein. On the other hand, several picornaviruses, cardioviruses included, have various types of leader (L) proteins marking the beginnings of their reading frames. In some instances, e.g., in aphthoviruses, the L proteins possess protease activity (}22, 68), whereas in others, e.g., cardioviruses, they do not exhibit proteolytic or any other known enzymatic activity. The actual function of L in the cardiovirus life cycle is yet to be defined, although it was reported that it might affect host translation (81), interferon response (19, 82; S. Hato et al., submitted for publication), and, in the case of TMEV, distribution of the proteins between the nucleus and cytoplasm (19).

An external file that holds a picture, illustration, etc.
Object name is zjv0060674810001.jpg

FIG. 1.

A schematic representation of picornavirus genomes. (A) The general structure of the genome, which harbors a single open reading frame, flanked with 5′ untranslated (5′UTR) and 3′ untranslated (3′UTR) regions terminated with a genome-linked viral protein VPg and poly(A) tail, respectively. (B) Differences in the organization of coding regions of some picornaviruses. Nonhomologous regions are differently hatched. Aphthoviruses contain three very similar, though not identical, copies of 3B (VPg)-coding sequences.

Taking into account the essential role of poliovirus 2A^{in triggering alterations of the nucleocytoplasmic traffic, on the one hand, and the absence of a homologous protein in cardioviruses, on the other hand, we decided to study whether EMCV infection is accompanied by similar alterations of the cellular infrastructure, and if so, what viral protein(s) may be involved. As reported here, two closely related EMCV strains do facilitate the bidirectional relocation of proteins between the nucleus and cytoplasm, and it is the L protein which is largely, if not entirely, responsible for this phenomenon.}

Acknowledgments

This study was supported by grants from the INTAS, Ludwig Institute for Cancer Research, Russian Foundation for Basic Research, and Scientific School Support Program. A.G.A. was supported by National Institutes of Health grant AI-17331 to A.C.P.

Acknowledgments

REFERENCES

References

1. Adam, S. A., S. R. Marr, and L. Gerace. 1990. Nuclear protein import in permeabilized mammalian cells requires soluble cytoplasmic factors. J. Cell Biol.111:807-816.
2. Agol, VI. 2002. Picornavirus genome: an overview, p. 127-148. In B. L. Semler and E. Wimmer (ed.), Molecular biology of picornaviruses. ASM Press, Washington, D.C.[Google Scholar]
3. Agol, V. I., G. A. Belov, K. Bienz, D. Egger, M. S. Kolesnikova, N. T. Raikhlin, L. I. Romanova, E. A. Smirnova, and E. A. Tolskaya. 1998. Two types of death of poliovirus-infected cells: caspase involvement in the apoptosis but not cytopathic effect. Virology252:343-353. [[PubMed]
4. Akiyama, T., J. Ishida, S. Nakagawa, H. Ogawara, S. Watanabe, N. Itoh, M. Shibuya, and Y. Fukami. 1987. Genistein, a specific inhibitor of tyrosine-specific protein kinases. J. Biol. Chem.262:5592-5595. [[PubMed]
5. Aminev, A. G., S. P. Amineva, and A. C. Palmenberg. 2003. Encephalomyocarditis viral protein 2A localizes to nucleoli and inhibits cap-dependent mRNA translation. Virus Res.95:45-57. [[PubMed]
6. Aminev, A. G., S. P. Amineva, and A. C. Palmenberg. 2003. Encephalomyocarditis virus (EMCV) proteins 2A and 3BCD localize to nuclei and inhibit cellular mRNA transcription but not rRNA transcription. Virus Res.95:59-73. [[PubMed]
7. Barton, D. J., and J. B. Flanegan. 1993. Coupled translation and replication of poliovirus RNA in vitro: synthesis of functional 3D polymerase and infectious virus. J. Virol.67:822-831.
8. Belov, G. A., A. G. Evstafieva, O. V. Mikitas, A. B. Vartapetian, and V. I. Agol. 2000. Early alteration of nucleocytoplasmic traffic induced by some RNA viruses. Virology275:244-248. [[PubMed]
9. Belov, G. A., L. I. Romanova, E. A. Tolskaya, M. S. Kolesnikova, Y. A. Lazebnik, and V. I. Agol. 2003. The major apoptotic pathway activated and suppressed by poliovirus. J. Virol.77:45-56.
10. Belov, G. A., P. V. Lidsky, O. V. Mikitas, D. Egger, K. A. Lukyanov, K. Bienz, and V. I. Agol. 2004. Bidirectional increase in permeability of nuclear envelope upon poliovirus infection and accompanying alterations of nuclear pores. J. Virol.78:10166-10177.
11. Bienz, K., D. Egger, Y. Rasser, and W. Bossart. 1982. Accumulation of poliovirus proteins in the host cell nucleus. Intervirology18:189-196. [[PubMed]
12. 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.
13. Bouyac-Bertoia, M., J. D. Dvorin, R. A. Fouchier, Y. Jenkins, B. E. Meyer, L. I. Wu, M. Emerman, and M. H. Malim. 2001. HIV-1 infection requires a functional integrase NLS. Mol. Cell7:1025-1035. [[PubMed]
14. Buendia, B., A. Santa-Maria, and J. C. Courvalin. 1999. Caspase-dependent proteolysis of integral and peripheral proteins of nuclear membranes and nuclear pore complex proteins during apoptosis. J. Cell Sci.112:1743-1753. [[PubMed]
15. Calenoff, M. A., C. S. Badshah, M. C. Dal Canto, H. L. Lipton, and M. K. Rundell. 1995. The leader polypeptide of Theiler's virus is essential for neurovirulence but not for virus growth in BHK cells. J. Virol.69:5544-5549.
16. 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.
17. Costa-Mattioli, M., Y. Svitkin, and N. Sonenberg. 2004. La autoantigen is necessary for optimal function of the poliovirus and hepatitis C virus internal ribosome entry site in vivo and in vitro. Mol. Cell. Biol.24:6861-6870.
18. Cros, J. F., and P. Palese. 2003. Trafficking of viral genomic RNA into and out of the nucleus: influenza, Thogoto and Borna disease viruses. Virus. Res.95:3-12. [[PubMed]
19. Delhaye, S., V. van Pesch, and T. Michiels. 2004. The leader protein of Theiler's virus interferes with nucleocytoplasmic trafficking of cellular proteins. J. Virol.78:4357-4362.
20. de Noronha, C. M. C., M. P. Sherman, H. W. Lin, M. V. Cavrois, R. D. Moir, R. D. Goldman, and W. C. Greene. 2001. Dynamic disruptions in nuclear envelope architecture and integrity induced by HIV-1 Vpr. Science294:1105-1108. [[PubMed]
21. Deszcz, L., J. Seipelt, E. Vassilieva, A. Roetzer, and E. Kuechler. 2004. Antiviral activity of caspase inhibitors: effect on picornaviral 2A proteinase. FEBS Lett.560:51-55. [[PubMed]
22. 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.
23. Dobner, T., and JKzhyshkowska. 2001. Nuclear export of adenovirus RNA. Curr. Top. Microbiol. Immunol.259:25-54. [[PubMed][Google Scholar]
24. Dvorak, C. M., D. J. Hall, M. Hill, M. Riddle, A. Pranter, J. Dillman, M. Deibel, and A. C. Palmenberg. 2001. Leader protein of encephalomyocarditis virus binds zinc, is phosphorylated during viral infection, and affects the efficiency of genome translation. Virology290:261-271. [[PubMed]
25. Fahrenkrog, B., and UAebi. 2003. The nuclear pore complex: nucleocytoplasmic transport and beyond. Nat. Rev. Mol. Cell. Biol.4:757-766. [[PubMed][Google Scholar]
26. Faleiro, L., and YLazebnik. 2000. Caspases disrupt the nuclear-cytoplasmic barrier. J. Cell Biol.151:951-959. [Google Scholar]
27. Feldherr, C., and DAkin. 1995. Stimulation of nuclear import by simian virus 40-transformed cell extracts is dependent on protein kinase activity. Mol. Cell. Biol.15:7043-7049. [Google Scholar]
28. Feldherr, C., D. Akin, and R. Cohen. 2001. Regulation of functional nuclear pore size in fibroblasts. J. Cell Sci.114:4621-4627. [[PubMed]
29. Fernandez-Tomas, C. 1982. The presence of viral-induced proteins in nuclei from poliovirus-infected HeLa cells. Virology116:629-634. [[PubMed]
30. Ferrando-May, E., V. Cordes, I. Biller-Ckovric, J. Mirkovic, D. Gorlich, and P. Nicotera. 2001. Caspases mediate nucleoporin cleavage, but not early redistribution of nuclear transport factors and modulation of nuclear permeability in apoptosis. Cell Death Differ.8:495-505. [[PubMed]
31. Follett, E. A., C. R. Pringle, and T. H. Pennington. 1975. Virus development in enucleate cells: echovirus, poliovirus, pseudorabies virus, reovirus, respiratory syncytial virus and Semliki Forest virus. J. Gen. Virol.26:183-196. [[PubMed]
32. Gorlich, D. 1997. Nuclear protein import. Curr. Opin. Cell Biol.9:412-419. [[PubMed]
33. Greber, U. F., and A. Fassati. 2003. Nuclear import of viral DNA genomes. Traffic4:136-143. [[PubMed]
34. Gustin, K. E., and P. Sarnow. 2001. Effects of poliovirus infection on nucleo-cytoplasmic trafficking and nuclear pore complex composition. EMBO J.20:240-249.
35. Gustin, K. E., and P. Sarnow. 2002. Inhibition of nuclear import and alteration of nuclear pore complex composition by rhinovirus. J. Virol.76:8787-8796.
36. Haffar, O. K., S. Popov, L. Dubrovsky, I. Agostini, H. Tang, T. Pushkarsky, S. G. Nadler, and M. Bukrinsky. 2000. Two nuclear localization signals in the HIV-1 matrix protein regulate nuclear import of the HIV-1 pre-integration complex. J. Mol. Biol.299:359-368. [[PubMed]
37. Hellen, C. U., G. W. Witherell, M. Schmid, S. H. Shin, T. V. Pestova, A. Gil, and E. Wimmer. 1993. A cytoplasmic 57-kDa protein that is required for translation of picornavirus RNA by internal ribosomal entry is identical to the nuclear pyrimidine tract-binding protein. Proc. Natl. Acad. Sci. USA90:7642-7646.
38. Henke, A., M. Nestler, S. Strunze, H. P. Saluz, P. Hortschansky, B. Menzel, U. Martin, R. Zell, A. Stelzner, and T. Munder. 2001. The apoptotic capability of coxsackievirus B3 is influenced by the efficient interaction between the capsid protein VP2 and the proapoptotic host protein Siva. Virology289:15-22. [[PubMed]
39. Hoyt, C. C., R. J. Bouchard, and K. L. Tyler. 2004. Novel nuclear herniations induced by nuclear localization of a viral protein. J. Virol.78:6360-6369.
40. Izumi, R. E., B. Valdez, R. Banerjee, M. Srivastava, and A. Dasgupta. 2001. Nucleolin stimulates viral internal ribosome entry site-mediated translation. Virus Res.76:17-29. [[PubMed]
41. Jelachich, M. L., and H. L. Lipton. 2001. Theiler's murine encephalomyelitis virus induces apoptosis in gamma interferon-activated M1 differentiated myelomonocytic cells through a mechanism involving tumor necrosis factor alpha (TNF-α) and TNF-αrelated apoptosis-inducing ligand. J. Virol.75:5930-5938.
42. 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.
43. Kann, M., B. Sodeik, A. Vlachou, W. H. Gerlich, and A. Helenius. 1999. Phosphorylation-dependent binding of hepatitis B virus core particles to the nuclear pore complex. J. Cell Biol.145:45-55.
44. König, H., and BRosenwirth. 1987. Purification and partial characterization of poliovirus protease 2A by means of a functional assay. J. Virol.62:1243-1250. [Google Scholar]
45. Lombardo, E., J. C. Ramírez, M. Agbandje-Mckenna, and J. M. Almendral. 2000. A β-stranded motif drives capsid protein oligomers of the parvovirus minute virus of mice into the nucleus for viral assembly. J. Virol.74:3804-3814.
46. Malim, M. H., J. Hauber, S. Y. Le, J. V. Maizel, and B. R. Cullen. 1989. The HIV-1 rev trans-activator acts through a structured target sequence to activate nuclear export of unspliced viral mRNA. Nature338:254-257. [[PubMed]
47. Margalit, A., S. Vlcek, Y. Gruenbaum, and R. Foisner. 2005. Breaking and making of the nuclear envelope. J. Cell. Biochem.95:454-465. [[PubMed]
48. McBride, A. E., A. Schlegel, and K. Kirkegaard. 1996. Human protein Sam68 relocalization and interaction with poliovirus RNA polymerase in infected cells. Proc. Natl. Acad. Sci. USA93:2296-2301.
49. Medvedkina, O. A., I. V. Scarlat, N. O. Kalinina, and V. I. Agol. 1974. Virus-specific proteins associated with ribosomes of Krebs-II cells infected with encephalomyocarditis virus. FEBS Lett.39:4-8. [[PubMed]
50. Meerovitch, K., Y. V. Svitkin, H. S. Lee, F. Lejbkowicz, D. J. Kenan, E. K. 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.67:3798-3807.
51. Meggio, F., D. Shugar, and L. A. Pinna. 1990. Ribofuranosyl-benzimidazole derivatives as inhibitors of casein kinase-2 and casein kinase-1. Eur. J. Biochem.187:89-94. [[PubMed]
52. Molla, A., A. V. Paul, and E. Wimmer. 1991. Cell-free, de novo synthesis of poliovirus. Science254:1647-1651. [[PubMed]
53. Molla, A., C. U. Hellen, and E. Wimmer. 1993. Inhibition of proteolytic activity of poliovirus and rhinovirus 2A proteinases by elastase-specific inhibitors. J. Virol.67:4688-4695.
54. Neznanov. N., K. M. Chumakov, L. Neznanova, A. Almasan, A. K. Banerjee, and A. V. Gudkov. 2005. Proteolytic cleavage of the p65-RelA subunit of NF-kappa B during poliovirus infection. J. Biol. Chem.280:24153-24158. [[PubMed]
55. Pemberton, L. F., and B. M. Paschal. 2005. Mechanisms of receptor- mediated nuclear import and nuclear export. Traffic6:187-198. [[PubMed]
56. Peng, J. M., S. M. Liang, and C. M. Liang. 2004. VP1 of foot-and-mouth disease virus induces apoptosis via the Akt signaling pathway. J. Biol. Chem.279:52168-52174. [[PubMed]
57. Petersen, J. M., L. S. Her, V. Varvel, E. Lund, and J. E. Dahlberg. 2000. The matrix protein of vesicular stomatitis virus inhibits nucleocytoplasmic transport when it is in the nucleus and associated with nuclear pore complexes. Mol. Cell. Biol.20:8590-8601.
58. 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. Cell68:119-131. [[PubMed]
59. Pilipenko, E. V., T. V. Pestova, V. G. Kolupaeva, E. V. Khitrina, A. N. Poperechnaya, V. I. Agol, and C. U. Hellen. 2000. A cell cycle-dependent protein serves as a template-specific translation initiation factor. Genes Dev.14:2028-2045.
60. Pollack, R., and RGoldman. 1973. Synthesis of infective poliovirus in BSC-1 monkey cells enucleated with cytochalasin B. Science179:915-916. [[PubMed][Google Scholar]
61. Rabe, B., A. Vlachou, N. Panté, A. Helenius, and M. Kann. 2003. Nuclear import of hepatitis B capsids and release of the viral genome. Proc. Natl. Acad. Sci. USA100:9849-9854.
62. Ruegg, U. T., and G. M. Burgess. 1989. Staurosporine, K-252 and UCN-01: potent but nonspecific inhibitors of protein kinases. Trends Pharmacol. Sci.10:218-220. [[PubMed]
63. Sandri-Goldin, RM. 2001. Nuclear export of herpes virus RNA. Curr. Top. Microbiol. Immunol.259:2-23. [[PubMed][Google Scholar]
64. Semler, B. L., and E. Wimmer (ed.). 2002. Molecular biology of picornaviruses. American Society for Microbiology, Washington, D.C.
65. Sharma, R., S. Raychaudhuri, and A. Dasgupta. 2004. Nuclear entry of poliovirus protease-polymerase precursor 3CD: implications for host cell transcription shut-off. Virology320:195-205. [[PubMed]
66. Shen, Y., M. Igo, P. Yalamanchili, A. J. Berk, and A. Dasgupta. 1996. DNA binding domain and subunit interactions of transcription factor IIIC revealed by dissection with poliovirus 3C protease. Mol. Cell. Biol.16:4163-4171.
67. Shiroki, K., T. Isoyama, S. Kuge, T. Ishii, S. Ohmi, S. Hata, K. Suzuki, Y. Takasaki, and A. Nomoto. 1999. Intracellular redistribution of truncated La protein produced by poliovirus 3C^{-mediated cleavage.}J. Virol.73:2193-2200.
68. Strebel, K., and EBeck. 1986. A second protease of foot-and-mouth disease virus. J. Virol.58:893-899. [Google Scholar]
69. Svitkin, Y. V., K. Meerovitch, H. S. Lee, J. N. Dholakia, D. J. Kenan, V. I. Agol, and N. Sonenberg. 1994. Internal translation initiation on poliovirus RNA: further characterization of La function in poliovirus translation in vitro. J. Virol.68:1544-1550.
70. Svitkin, Y. V., H. Imataka, K. Khaleghpour, A. Kahvejian, H. D. Liebig, and N. Sonenberg. 2001. Poly(A)-binding protein interaction with elF4G stimulates picornavirus IRES-dependent translation. RNA7:1743-1752.
71. Svitkin, Y. V., and N. Sonenberg. 2003. Cell-free synthesis of encephalomyocarditis virus. J. Virol.77:6551-6555.
72. Terskikh, A., A. Fradkov, G. Ermakova, A. Zaraisky, P. Tan, A. V. Kajava, X. Zhao, S. Lukyanov, M. Matz, S. Kim, I. Weissman, and P. Siebert. 2000. “Fluorescent timer”: protein that changes color with time. Science290:1585-1588. [[PubMed]
73. Tolskaya, E. A., L. I. Romanova, M. S. Kolesnikova, T. A. Ivannikova, E. A. Smirnova, N. T. Raikhlin, and V. I. Agol. 1995. Apoptosis-inducing and apoptosis-preventing functions of poliovirus. J. Virol.69:1181-1189.
74. Waggoner, S., and PSarnow. 1998. Viral ribonucleoprotein complex formation and nucleolar-cytoplasmic relocalization of nucleolin in poliovirus-infected cells. J. Virol.72:6699-6709. [Google Scholar]
75. Weidman, M. K., R. Sharma, S. Raychaudhuri, P. Kundu, W. Tsai, and A. Dasgupta. 2003. The interaction of cytoplasmic RNA viruses with the nucleus. Virus Res.95:75-85. [[PubMed]
76. Welsh, J. D., C. Swimmer, T. Cocke, and T. Shenk. 1986. A second domain of simian virus 40 T antigen in which mutations can alter the cellular localization of the antigen. Mol. Cell. Biol.6:2207-2212.
77. Whittaker, G., M. Bui, and A. Helenius. 1996. The role of nuclear import and export in influenza virus infection. Trends Cell Biol.6:67-71. [[PubMed]
78. Yalamanchili, P., R. Banerjee, and A. Dasgupta. 1997. Poliovirus-encoded protease 2APro cleaves the TATA-binding protein but does not inhibit host cell RNA polymerase II transcription in vitro. J. Virol.71:6881-6886.
79. Yalamanchili, P., U. Datta, and A. Dasgupta. 1997. Inhibition of host cell transcription by poliovirus: cleavage of transcription factor CREB by poliovirus-encoded protease 3Cpro. J. Virol.71:1220-1226.
80. Yalamanchili, P., K. Weidman, and A. Dasgupta. 1997. Cleavage of transcriptional activator Oct-1 by poliovirus encoded protease 3Cpro. Virology239:176-185. [[PubMed]
81. Zoll, J., J. M. Galama, F. J. van Kuppeveld, and W. J. Melchers. 1996. Mengovirus leader is involved in the inhibition of host cell protein synthesis. J. Virol.70:4948-4952.
82. Zoll, J., W. J. Melchers, J. M. Galama, and F. J. van Kuppeveld. 2002. The mengovirus leader protein suppresses alpha/beta interferon production by inhibition of the iron/ferritin-mediated activation of NF-κB. J. Virol.76:9664-9672.