Principles of Virology. Jane Flint

AA, Brinton MA. 2018. New insights about the regulation of Nidovirus subgenomic mRNA synthesis. Virology 517:38–43.

      Ferrero D, Ferrer-Orta C, Verdaguer N. 2018. Viral RNA-dependent RNA polymerases: a structural overview. Subcell Biochem 88:39–71.

      Flores R, Grubb D, Elleuch A, Nohales MÁ, Delgado S, Gago S. 2011. Rolling-circle replication of viroids, viroid-like satellite RNAs and hepatitis delta virus: variations on a theme. RNA Biol 8:200–206.

      Lo CY, Tang YS, Shaw PC. 2018. Structure and function of influenza virus ribonucleoprotein. Subcell Biochem 88:95–128.

      McDonald SM, Tao YJ, Patton JT. 2009. The ins and outs of four-tunneled Reoviridae RNA-dependent RNA polymerases. Curr Opin Struct Biol 19:775–782.

      Morin B, Kranzusch PJ, Rahmeh AA, Whelan SPJ. 2013. The polymerase of negative-stranded RNA viruses. Curr Opin Virol 3:103–110.

      Peersen OB. 2017. Picornaviral polymerase structure, function, and fidelity modulation. Virus Res 234:4–20.

      Steil BP, Barton DJ. 2009. Cis-active RNA elements (CREs) and picornavirus RNA replication. Virus Res 139:240–252.

       Papers of Special Interest

      Appleby TC, Perry JK, Murakami E, Barauskas O, Feng J, Cho A, Fox D, III, Wetmore DR, McGrath ME, Ray AS, Sofia MJ, Swaminathan S, Edwards TE. 2015. Viral replication. Structural basis for RNA replication by the hepatitis C virus polymerase. Science 347:771–775.

       Structure of the hepatitis C virus RNA polymerase reveals that highly conserved active-site residues position the primer for attack on the incoming nucleotide.

      Arranz R, Coloma R, Chichón FJ, Conesa JJ, Carrascosa JL, Valpuesta JM, Ortín J, Martín-Benito J. 2012. The structure of native influenza virion ribonucleoproteins. Science 338:1634–1637.

       Structure of RNPs from virus particles reveals a double-helical conformation in which two strands of opposite polarity are associated along the helix.

      Gallagher JR, Torian U, McCraw DM, Harris AK. 2017. Structural studies of influenza virus RNPs by electron microscopy indicate molecular contortions within NP supra-structures. J Struct Biol 197:294–307.

       The use of electron tomography and image analysis reveals that isolate RNP filaments are not rigid helical structures.

      Gong P, Peersen OB. 2010. Structural basis for active site closure by the poliovirus RNA-dependent RNA polymerase. Proc Natl Acad Sci U S A 107:22505–22510.

       Structures of poliovirus RdRP reveal a pre-positioned templating base for nucleotide recognition, and a structural rearrangement in the palm domain leads to closure of catalytically active sites.

      Kempf BJ, Watkins CL, Peersen OB, Barton DJ. 2019. Picornavirus RNA recombination counteracts error catastrophe. J Virol 93:e00652–e19.

       Picornavirus RNA recombination counteracts the negative consequences of error-prone RNA replication.

      Kirchdoerfer RN, Saphire EO, Ward AB. 2019. Cryo-EM structure of the Ebola virus nucleoprotein-RNA complex. Acta Crystallogr F Struct Biol Commun 75:340–347.

       High-resolution structure reveals details of protein-protein and protein-RNA interactions.

      Liang B, Li Z, Jenni S, Rahmeh AA, Morin BM, Grant T, Grigorieff N, Harrison SC, Whelan SPJ. 2015. Structure of the L protein of vesicular stomatitis virus from electron cryomicroscopy. Cell 162:314–327.

       Structure of the L protein reveals a core RNA polymerase, an mRNA capping domain, and a methyltransferase domain.

      Matsumoto Y, Ohta K, Kolakofsky D, Nishio M. 2018. The control of paramyxovirus genome hexamer length and mRNA editing. RNA 24:461–467.

       How the requirement for genome hexamer length, bipartite replication promoters, and P gene mRNA editing are linked among paramyxoviruses.

      Moeller A, Kirchdoerfer RN, Potter CS, Carragher B, Wilson IA. 2012. Organization of the influenza virus replication machinery. Science 338: 1631–1634.

       Cryo-electron microscopy structure of influenza virus RNP reveals architecture and organization of the native complex.

      Pflug A, Guilligay D, Reich S, Cusack S. 2014. Structure of influenza A polymerase bound to the viral RNA promoter. Nature 516:355–360.

       Crystal structure of trimeric influenza viral RdRP bound to its promoter, revealing mechanisms of activation and cap snatching.

      Reich S, Guilligay D, Pflug A, Malet H, Berger I, Crépin T, Hart D, Lunardi T, Nanao M, Ruigrok RW, Cusack S. 2014. Structural insight into cap-snatching and RNA synthesis by influenza polymerase. Nature 516: 361–366.

       Structures of influenza virus RNA polymerase bound to viral RNA provide mechanistic insight into the different processes of mRNA synthesis and genome RNA replication.

      Subissi L, Posthuma CC, Collet A, Zevenhoven-Dobbe JC, Gorbalenya AE, Decroly E, Snijder EJ, Canard B, Imbert I. 2014. One severe acute respiratory syndrome coronavirus protein complex integrates processive RNA polymerase and exonuclease activities. Proc Natl Acad Sci U S A 111:E3900– E3909.

       Identification of a tripartite polymerase complex associated with the viral proofreading enzyme.

STUDY QUESTIONS

      1 Which of the following statements concerning viral RNA synthesis is incorrect?The RNA genome must be copied end to endmRNAs must be produced that can be translated by the cellRNA polymerases were first identified by labeling cells with radioactive precursorsA positive-strand viral RNA must enter the cell together with an RNA polymeraseA viral RNA polymerase copies the viral RNA genome

      2 Consider a virus with a (+) strand RNA genome 8 kb in length, which encodes eight proteins. Which of the following is a known mechanism for producing all eight proteins from this genome?A single polyprotein is synthesized, which is then processed by proteases to form eight proteinsThe RNA is cleaved into eight fragments, each of which is translated into a different proteinImmediately upon entering the cells, the viral RNA polymerase that is carried into the cell within the virus particle produces eight subgenomic mRNAs from the (+) strand RNA genomeThere is no way to produce multiple proteins from a eukaryotic RNA

      3 Which situation best illustrates the finding that for some viruses, the nucleic acid does not leave the particle?Cap snatching during the production of influenza viral mRNAsPolyadenylation by slippage of RNA polymerase at intergenic sequences on the templateSynthesis of reovirus mRNAsVPg priming of polioviral RNA synthesis

      4 Virus particles of (–) strand RNA viruses contain an RNA-dependent RNA polymerase. Virus particles of (+) strand RNA viruses (except retroviruses) do not contain an RNA-dependent RNA polymerase. As cells do not have RNA-dependent RNA polymerase, where does the RNA polymerase of (+) strand RNA viruses come from?

      5 You purify all the influenza virus mRNAs from an infected cell. When you transfect these influenza viral mRNAs into a permissive cell, no infectious virus is produced. Why are the influenza viral mRNAs not infectious?

      6 Before