Novel Roles of the Picornaviral 3D Polymerase in Viral Pathogenesis

Overview

Journal Adv Virol

Publisher Wiley

Specialty Microbiology

Date 2010 Jul 14

PMID 20625447

Citations 1

Authors

Jason Kerkvliet

Ramakrishna Edukulla

Moses Rodriguez

Affiliations

Soon will be listed here.

Abstract

The RNA-dependent RNA-polymerase, 3D(pol), is an essential component in the picornavirus genome for the replication of single stranded RNA. However, transgenic expression of 3D(pol) in mice has antiviral effects. Here we discuss the structure and function of 3D(pol) during picornavirus replication, we review the evidence and consequence of a host immune response to epitopes in 3D(pol) after picornavirus infection, highlight data showing the antiviral effects of transgenic 3D(pol) from Theiler's murine encephalomyelitis virus (TMEV), and discuss potential mechanisms by which 3D(pol) is causing this antiviral effect in mice.

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References

Lama J, Paul A, Harris K, Wimmer E . Properties of purified recombinant poliovirus protein 3aB as substrate for viral proteinases and as co-factor for RNA polymerase 3Dpol. J Biol Chem. 1994; 269(1):66-70. View

Amineva S, Aminev A, Palmenberg A, Gern J . Rhinovirus 3C protease precursors 3CD and 3CD' localize to the nuclei of infected cells. J Gen Virol. 2004; 85(Pt 10):2969-2979. DOI: 10.1099/vir.0.80164-0. View

Samuel C . Antiviral actions of interferons. Clin Microbiol Rev. 2001; 14(4):778-809, table of contents. PMC: 89003. DOI: 10.1128/CMR.14.4.778-809.2001. View

Hansen J, Long A, SCHULTZ S . Structure of the RNA-dependent RNA polymerase of poliovirus. Structure. 1997; 5(8):1109-22. DOI: 10.1016/s0969-2126(97)00261-x. View

Appleby T, Luecke H, Shim J, Wu J, Cheney I, Zhong W . Crystal structure of complete rhinovirus RNA polymerase suggests front loading of protein primer. J Virol. 2004; 79(1):277-88. PMC: 538717. DOI: 10.1128/JVI.79.1.277-288.2005. View

Franklin R, Baltimore D . Patterns of macromolecular synthesis in normal and virus-infected mammalian cells. Cold Spring Harb Symp Quant Biol. 1962; 27:175-98. DOI: 10.1101/sqb.1962.027.001.019. View

Azoulay A, Brahic M, Bureau J . FVB mice transgenic for the H-2Db gene become resistant to persistent infection by Theiler's virus. J Virol. 1994; 68(6):4049-52. PMC: 236915. DOI: 10.1128/JVI.68.6.4049-4052.1994. View

Shen M, Reitman Z, Zhao Y, Moustafa I, Wang Q, Arnold J . Picornavirus genome replication. Identification of the surface of the poliovirus (PV) 3C dimer that interacts with PV 3Dpol during VPg uridylylation and construction of a structural model for the PV 3C2-3Dpol complex. J Biol Chem. 2007; 283(2):875-88. PMC: 2186065. DOI: 10.1074/jbc.M707907200. View

Pata J, SCHULTZ S, Kirkegaard K . Functional oligomerization of poliovirus RNA-dependent RNA polymerase. RNA. 1995; 1(5):466-77. PMC: 1482417. View

10.

Campagnola G, Weygandt M, Scoggin K, Peersen O . Crystal structure of coxsackievirus B3 3Dpol highlights the functional importance of residue 5 in picornavirus polymerases. J Virol. 2008; 82(19):9458-64. PMC: 2546958. DOI: 10.1128/JVI.00647-08. View

11.

Ferrer-Orta C, Arias A, Perez-Luque R, Escarmis C, Domingo E, Verdaguer N . Structure of foot-and-mouth disease virus RNA-dependent RNA polymerase and its complex with a template-primer RNA. J Biol Chem. 2004; 279(45):47212-21. DOI: 10.1074/jbc.M405465200. View

12.

Pathak H, Arnold J, Wiegand P, Hargittai M, Cameron C . Picornavirus genome replication: assembly and organization of the VPg uridylylation ribonucleoprotein (initiation) complex. J Biol Chem. 2007; 282(22):16202-13. PMC: 2116992. DOI: 10.1074/jbc.M610608200. View

13.

Sharma R, Raychaudhuri S, Dasgupta A . Nuclear entry of poliovirus protease-polymerase precursor 3CD: implications for host cell transcription shut-off. Virology. 2004; 320(2):195-205. DOI: 10.1016/j.virol.2003.10.020. View

14.

Murray K, Barton D . Poliovirus CRE-dependent VPg uridylylation is required for positive-strand RNA synthesis but not for negative-strand RNA synthesis. J Virol. 2003; 77(8):4739-50. PMC: 152113. DOI: 10.1128/jvi.77.8.4739-4750.2003. View

15.

Altschul S, Wootton J, Gertz E, Agarwala R, Morgulis A, Schaffer A . Protein database searches using compositionally adjusted substitution matrices. FEBS J. 2005; 272(20):5101-9. PMC: 1343503. DOI: 10.1111/j.1742-4658.2005.04945.x. View

16.

Strauss D, Wuttke D . Characterization of protein-protein interactions critical for poliovirus replication: analysis of 3AB and VPg binding to the RNA-dependent RNA polymerase. J Virol. 2007; 81(12):6369-78. PMC: 1900118. DOI: 10.1128/JVI.02252-06. View

17.

Paul A, Cao X, Harris K, Lama J, Wimmer E . Studies with poliovirus polymerase 3Dpol. Stimulation of poly(U) synthesis in vitro by purified poliovirus protein 3AB. J Biol Chem. 1994; 269(46):29173-81. View

18.

RICHARDS O, EHRENFELD E . Effects of poliovirus 3AB protein on 3D polymerase-catalyzed reaction. J Biol Chem. 1998; 273(21):12832-40. DOI: 10.1074/jbc.273.21.12832. View

19.

Patick A, Pease L, David C, Rodriguez M . Major histocompatibility complex-conferred resistance to Theiler's virus-induced demyelinating disease is inherited as a dominant trait in B10 congenic mice. J Virol. 1990; 64(11):5570-6. PMC: 248609. DOI: 10.1128/JVI.64.11.5570-5576.1990. View

20.

Oh H, Pathak H, Goodfellow I, Arnold J, Cameron C . Insight into poliovirus genome replication and encapsidation obtained from studies of 3B-3C cleavage site mutants. J Virol. 2009; 83(18):9370-87. PMC: 2738245. DOI: 10.1128/JVI.02076-08. View