1887

Abstract

The members of the genus are positive-sense RNA viruses, which are predominantly transmitted to vertebrates by a mosquito vector. Alphavirus disease in humans can be severely debilitating, and depending on the particular viral species, infection may result in encephalitis and possibly death. In recent years, alphaviruses have received significant attention from public health authorities as a consequence of the dramatic emergence of chikungunya virus in the Indian Ocean islands and the Caribbean. Currently, no safe, approved or effective vaccine or antiviral intervention exists for human alphavirus infection. The molecular biology of alphavirus RNA synthesis has been well studied in a few species of the genus and represents a general target for antiviral drug development. This review describes what is currently understood about the regulation of alphavirus RNA synthesis, the roles of the viral non-structural proteins in this process and the functions of acting RNA elements in replication, and points to open questions within the field.

Loading

Article metrics loading...

/content/journal/jgv/10.1099/jgv.0.000249
2015-09-01
2020-01-23
Loading full text...

Full text loading...

/deliver/fulltext/jgv/96/9/2483.html?itemId=/content/journal/jgv/10.1099/jgv.0.000249&mimeType=html&fmt=ahah

References

  1. Aaskov J. , Jones A. , Choi W. , Lowry K. , Stewart E. . ( 2011;). Lineage replacement accompanying duplication and rapid fixation of an RNA element in the nsP3 gene in a species of alphavirus. Virology 410: 353–359 [CrossRef] [PubMed].
    [Google Scholar]
  2. Ahola T. , Kääriäinen L. . ( 1995;). Reaction in alphavirus mRNA capping: formation of a covalent complex of nonstructural protein nsP1 with 7-methyl-GMP. Proc Natl Acad Sci U S A 92: 507–511 [CrossRef] [PubMed].
    [Google Scholar]
  3. Ahola T. , Karlin D.G. . ( 2015;). Sequence analysis reveals a conserved extension in the capping enzyme of the alphavirus supergroup, and a homologous domain in nodaviruses. Biol Direct 10: 16 [CrossRef] [PubMed].
    [Google Scholar]
  4. Ahola T. , Laakkonen P. , Vihinen H. , Kääriäinen L. . ( 1997;). Critical residues of Semliki Forest virus RNA capping enzyme involved in methyltransferase and guanylyltransferase-like activities. J Virol 71: 392–397 [PubMed].
    [Google Scholar]
  5. Ahola T. , Lampio A. , Auvinen P. , Kääriäinen L. . ( 1999;). Semliki Forest virus mRNA capping enzyme requires association with anionic membrane phospholipids for activity. EMBO J 18: 3164–3172 [CrossRef] [PubMed].
    [Google Scholar]
  6. Ahola T. , Kujala P. , Tuittila M. , Blom T. , Laakkonen P. , Hinkkanen A. , Auvinen P. . ( 2000;). Effects of palmitoylation of replicase protein nsP1 on alphavirus infection. J Virol 74: 6725–6733 [CrossRef] [PubMed].
    [Google Scholar]
  7. Akhrymuk I. , Kulemzin S.V. , Frolova E.I. . ( 2012;). Evasion of the innate immune response: the Old World alphavirus nsP2 protein induces rapid degradation of Rpb1, a catalytic subunit of RNA polymerase II. J Virol 86: 7180–7191 [CrossRef] [PubMed].
    [Google Scholar]
  8. Allen M.D. , Buckle A.M. , Cordell S.C. , Löwe J. , Bycroft M. . ( 2003;). The crystal structure of AF1521 a protein from Archaeoglobus fulgidus with homology to the non-histone domain of macroH2A. J Mol Biol 330: 503–511 [CrossRef] [PubMed].
    [Google Scholar]
  9. Atasheva S. , Gorchakov R. , English R. , Frolov I. , Frolova E. . ( 2007;). Development of Sindbis viruses encoding nsP2/GFP chimeric proteins and their application for studying nsP2 functioning. J Virol 81: 5046–5057 [CrossRef] [PubMed].
    [Google Scholar]
  10. Barton D.J. , Sawicki S.G. , Sawicki D.L. . ( 1991;). Solubilization and immunoprecipitation of alphavirus replication complexes. J Virol 65: 1496–1506 [PubMed].
    [Google Scholar]
  11. Büchen-Osmond C.E. . ( 2006;). In: ICTVdB - The Universal Virus Database, version 4. Online: Columbia University, New York, USA http://www.ncbi.nlm.nih.gov/ICTVdb/Ictv/fs_index.htm .
  12. Burnham A.J. , Gong L. , Hardy R.W. . ( 2007;). Heterogeneous nuclear ribonuclear protein K interacts with Sindbis virus nonstructural proteins and viral subgenomic mRNA. Virology 367: 212–221 [CrossRef] [PubMed].
    [Google Scholar]
  13. Chen R. , Wang E. , Tsetsarkin K.A. , Weaver S.C. . ( 2013;). Chikungunya virus 3′ untranslated region: adaptation to mosquitoes and a population bottleneck as major evolutionary forces. PLoS Pathog 9: e1003591 [CrossRef] [PubMed].
    [Google Scholar]
  14. Cheng R.H. , Kuhn R.J. , Olson N.H. , Rossmann M.G. , Choi H.K. , Smith T.J. , Baker T.S. . ( 1995;). Nucleocapsid and glycoprotein organization in an enveloped virus. Cell 80: 621–630 [CrossRef] [PubMed].
    [Google Scholar]
  15. Chung B.Y. , Firth A.E. , Atkins J.F. . ( 2010;). Frameshifting in alphaviruses: a diversity of 3′ stimulatory structures. J Mol Biol 397: 448–456 [CrossRef] [PubMed].
    [Google Scholar]
  16. Cristea I.M. , Carroll J.-W.N. , Rout M.P. , Rice C.M. , Chait B.T. , MacDonald M.R. . ( 2006;). Tracking and elucidating alphavirus-host protein interactions. J Biol Chem 281: 30269–30278 [CrossRef] [PubMed].
    [Google Scholar]
  17. Cristea I.M. , Rozjabek H. , Molloy K.R. , Karki S. , White L.L. , Rice C.M. , Rout M.P. , Chait B.T. , MacDonald M.R. . ( 2010;). Host factors associated with the Sindbis virus RNA-dependent RNA polymerase: role for G3BP1 and G3BP2 in virus replication. J Virol 84: 6720–6732 [CrossRef] [PubMed].
    [Google Scholar]
  18. Cross R.K. . ( 1983;). Identification of a unique guanine-7-methyltransferase in Semliki Forest virus (SFV) infected cell extracts. Virology 130: 452–463 [CrossRef] [PubMed].
    [Google Scholar]
  19. Cruz C.C. , Suthar M.S. , Montgomery S.A. , Shabman R. , Simmons J. , Johnston R.E. , Morrison T.E. , Heise M.T. . ( 2010;). Modulation of type I IFN induction by a virulence determinant within the alphavirus nsP1 protein. Virology 399: 1–10 [CrossRef] [PubMed].
    [Google Scholar]
  20. Daffis S. , Szretter K.J. , Schriewer J. , Li J. , Youn S. , Errett J. , Lin T.Y. , Schneller S. , Zust R. , other authors . ( 2010;). 2′-O methylation of the viral mRNA cap evades host restriction by IFIT family members. Nature 468: 452–456 [CrossRef] [PubMed].
    [Google Scholar]
  21. Das P.K. , Merits A. , Lulla A. . ( 2014;). Functional cross-talk between distant domains of chikungunya virus non-structural protein 2 is decisive for its RNA-modulating activity. J Biol Chem 289: 5635–5653 [CrossRef] [PubMed].
    [Google Scholar]
  22. Davis N.L. , Willis L.V. , Smith J.F. , Johnston R.E. . ( 1989;). In vitro synthesis of infectious venezuelan equine encephalitis virus RNA from a cDNA clone: analysis of a viable deletion mutant. Virology 171: 189–204 [CrossRef] [PubMed].
    [Google Scholar]
  23. I. , Sawicki S.G. , Sawicki D.L. . ( 1996;). Sindbis virus RNA-negative mutants that fail to convert from minus-strand to plus-strand synthesis: role of the nsP2 protein. J Virol 70: 2706–2719 [PubMed].
    [Google Scholar]
  24. I. , Fata-Hartley C. , Sawicki S.G. , Sawicki D.L. . ( 2003;). Functional analysis of nsP3 phosphoprotein mutants of Sindbis virus. J Virol 77: 13106–13116 [CrossRef] [PubMed].
    [Google Scholar]
  25. de Groot R.J. , Hardy W.R. , Shirako Y. , Strauss J.H. . ( 1990;). Cleavage-site preferences of Sindbis virus polyproteins containing the non-structural proteinase. Evidence for temporal regulation of polyprotein processing in vivo . EMBO J 9: 2631–2638 [PubMed].
    [Google Scholar]
  26. de Groot R.J. , Rümenapf T. , Kuhn R.J. , Strauss E.G. , Strauss J.H. . ( 1991;). Sindbis virus RNA polymerase is degraded by the N-end rule pathway. Proc Natl Acad Sci U S A 88: 8967–8971 [CrossRef] [PubMed].
    [Google Scholar]
  27. Egloff M.P. , Malet H. , Putics A. , Heinonen M. , Dutartre H. , Frangeul A. , Gruez A. , Campanacci V. , Cambillau C. , other authors . ( 2006;). Structural and functional basis for ADP-ribose and poly(ADP-ribose) binding by viral macro domains. J Virol 80: 8493–8502 [CrossRef] [PubMed].
    [Google Scholar]
  28. Fata C.L. , Sawicki S.G. , Sawicki D.L. . ( 2002a;). Alphavirus minus-strand RNA synthesis: identification of a role for Arg183 of the nsP4 polymerase. J Virol 76: 8632–8640 [CrossRef] [PubMed].
    [Google Scholar]
  29. Fata C.L. , Sawicki S.G. , Sawicki D.L. . ( 2002b;). Modification of Asn374 of nsP1 suppresses a Sindbis virus nsP4 minus-strand polymerase mutant. J Virol 76: 8641–8649 [CrossRef] [PubMed].
    [Google Scholar]
  30. Fayzulin R. , Frolov I. . ( 2004;). Changes of the secondary structure of the 5′ end of the Sindbis virus genome inhibit virus growth in mosquito cells and lead to accumulation of adaptive mutations. J Virol 78: 4953–4964 [CrossRef] [PubMed].
    [Google Scholar]
  31. Firth A.E. , Chung B.Y. , Fleeton M.N. , Atkins J.F. . ( 2008;). Discovery of frameshifting in Alphavirus 6K resolves a 20-year enigma. Virol J 5: 108 [CrossRef] [PubMed].
    [Google Scholar]
  32. Firth A.E. , Wills N.M. , Gesteland R.F. , Atkins J.F. . ( 2011;). Stimulation of stop codon readthrough: frequent presence of an extended 3′ RNA structural element. Nucleic Acids Res 39: 6679–6691 [CrossRef] [PubMed].
    [Google Scholar]
  33. Forrester N.L. , Palacios G. , Tesh R.B. , Savji N. , Guzman H. , Sherman M. , Weaver S.C. , Lipkin W.I. . ( 2012;). Genome-scale phylogeny of the alphavirus genus suggests a marine origin. J Virol 86: 2729–2738 [CrossRef] [PubMed].
    [Google Scholar]
  34. Foy N.J. , Akhrymuk M. , Akhrymuk I. , Atasheva S. , Bopda-Waffo A. , Frolov I. , Frolova E.I. . ( 2013a;). Hypervariable domains of nsP3 proteins of New World and Old World alphaviruses mediate formation of distinct, virus-specific protein complexes. J Virol 87: 1997–2010 [CrossRef] [PubMed].
    [Google Scholar]
  35. Foy N.J. , Akhrymuk M. , Shustov A.V. , Frolova E.I. , Frolov I. . ( 2013b;). Hypervariable domain of nonstructural protein nsP3 of Venezuelan equine encephalitis virus determines cell-specific mode of virus replication. J Virol 87: 7569–7584 [CrossRef] [PubMed].
    [Google Scholar]
  36. Frey T.K. , Gard D.L. , Strauss J.H. . ( 1979;). Biophysical studies on circle formation by Sindbis virus 49 S RNA. J Mol Biol 132: 1–18 [CrossRef] [PubMed].
    [Google Scholar]
  37. Friedman R.M. , Levin J.G. , Grimley P.M. , Berezesky I.K. . ( 1972;). Membrane-associated replication complex in arbovirus infection. J Virol 10: 504–515 [PubMed].
    [Google Scholar]
  38. Frolov I. , Schlesinger S. . ( 1996;). Translation of Sindbis virus mRNA: analysis of sequences downstream of the initiating AUG codon that enhance translation. J Virol 70: 1182–1190 [PubMed].
    [Google Scholar]
  39. Frolov I. , Agapov E. , Hoffman T.A. Jr , Prágai B.M. , Lippa M. , Schlesinger S. , Rice C.M. . ( 1999;). Selection of RNA replicons capable of persistent noncytopathic replication in mammalian cells. J Virol 73: 3854–3865 [PubMed].
    [Google Scholar]
  40. Frolov I. , Hardy R. , Rice C.M. . ( 2001;). Cis-acting RNA elements at the 5′ end of Sindbis virus genome RNA regulate minus- and plus-strand RNA synthesis. RNA 7: 1638–1651 [CrossRef] [PubMed].
    [Google Scholar]
  41. Frolova E. , Frolov I. , Schlesinger S. . ( 1997;). Packaging signals in alphaviruses. J Virol 71: 248–258 [PubMed].
    [Google Scholar]
  42. Frolova E. , Gorchakov R. , Garmashova N. , Atasheva S. , Vergara L.A. , Frolov I. . ( 2006;). Formation of nsP3-specific protein complexes during Sindbis virus replication. J Virol 80: 4122–4134 [CrossRef] [PubMed].
    [Google Scholar]
  43. Frolova E.I. , Gorchakov R. , Pereboeva L. , Atasheva S. , Frolov I. . ( 2010;). Functional Sindbis virus replicative complexes are formed at the plasma membrane. J Virol 84: 11679–11695 [CrossRef] [PubMed].
    [Google Scholar]
  44. Fros J.J. , Domeradzka N.E. , Baggen J. , Geertsema C. , Flipse J. , Vlak J.M. , Pijlman G.P. . ( 2012;). Chikungunya virus nsP3 blocks stress granule assembly by recruitment of G3BP into cytoplasmic foci. J Virol 86: 10873–10879 [CrossRef] [PubMed].
    [Google Scholar]
  45. Froshauer S. , Kartenbeck J. , Helenius A. . ( 1988;). Alphavirus RNA replicase is located on the cytoplasmic surface of endosomes and lysosomes. J Cell Biol 107: 2075–2086 [CrossRef] [PubMed].
    [Google Scholar]
  46. Galbraith S.E. , Sheahan B.J. , Atkins G.J. . ( 2006;). Deletions in the hypervariable domain of the nsP3 gene attenuate Semliki Forest virus virulence. J Gen Virol 87: 937–947 [CrossRef] [PubMed].
    [Google Scholar]
  47. Garmashova N. , Gorchakov R. , Frolova E. , Frolov I. . ( 2006;). Sindbis virus nonstructural protein nsP2 is cytotoxic and inhibits cellular transcription. J Virol 80: 5686–5696 [CrossRef] [PubMed].
    [Google Scholar]
  48. Garmashova N. , Gorchakov R. , Volkova E. , Paessler S. , Frolova E. , Frolov I. . ( 2007;). The Old World and New World alphaviruses use different virus-specific proteins for induction of transcriptional shutoff. J Virol 81: 2472–2484 [CrossRef] [PubMed].
    [Google Scholar]
  49. Garneau N.L. , Sokoloski K.J. , Opyrchal M. , Neff C.P. , Wilusz C.J. , Wilusz J. . ( 2008;). The 3′ untranslated region of sindbis virus represses deadenylation of viral transcripts in mosquito and mammalian cells. J Virol 82: 880–892 [CrossRef] [PubMed].
    [Google Scholar]
  50. George J. , Raju R. . ( 2000;). Alphavirus RNA genome repair and evolution: molecular characterization of infectious sindbis virus isolates lacking a known conserved motif at the 3′ end of the genome. J Virol 74: 9776–9785 [CrossRef] [PubMed].
    [Google Scholar]
  51. Gomatos P.J. , Kääriäinen L. , Keränen S. , Ranki M. , Sawicki D.L. . ( 1980;). Semliki Forest virus replication complex capable of synthesizing 42S and 26S nascent RNA chains. J Gen Virol 49: 61–69 [CrossRef] [PubMed].
    [Google Scholar]
  52. Gomez de Cedrón M. , Ehsani N. , Mikkola M.L. , García J.A. , Kääriäinen L. . ( 1999;). RNA helicase activity of Semliki Forest virus replicase protein NSP2. FEBS Lett 448: 19–22 [CrossRef] [PubMed].
    [Google Scholar]
  53. Gorbalenya A.E. , Koonin E.V. , Donchenko A.P. , Blinov V.M. . ( 1988;). A novel superfamily of nucleoside triphosphate-binding motif containing proteins which are probably involved in duplex unwinding in DNA and RNA replication and recombination. FEBS Lett 235: 16–24 [CrossRef] [PubMed].
    [Google Scholar]
  54. Gorchakov R. , Hardy R. , Rice C.M. , Frolov I. . ( 2004;). Selection of functional 5′ cis-acting elements promoting efficient sindbis virus genome replication. J Virol 78: 61–75 [CrossRef] [PubMed].
    [Google Scholar]
  55. Gorchakov R. , Frolova E. , Frolov I. . ( 2005;). Inhibition of transcription and translation in Sindbis virus-infected cells. J Virol 79: 9397–9409 [CrossRef] [PubMed].
    [Google Scholar]
  56. Gorchakov R. , Frolova E. , Sawicki S. , Atasheva S. , Sawicki D. , Frolov I. . ( 2008a;). A new role for ns polyprotein cleavage in Sindbis virus replication. J Virol 82: 6218–6231 [CrossRef] [PubMed].
    [Google Scholar]
  57. Gorchakov R. , Garmashova N. , Frolova E. , Frolov I. . ( 2008b;). Different types of nsP3-containing protein complexes in Sindbis virus-infected cells. J Virol 82: 10088–10101 [CrossRef] [PubMed].
    [Google Scholar]
  58. Grimley P.M. , Berezesky I.K. , Friedman R.M. . ( 1968;). Cytoplasmic structures associated with an arbovirus infection: loci of viral ribonucleic acid synthesis. J Virol 2: 1326–1338 [PubMed].
    [Google Scholar]
  59. Gui H. , Lu C.-W. , Adams S. , Stollar V. , Li M.-L. . ( 2010;). hnRNP A1 interacts with the genomic and subgenomic RNA promoters of Sindbis virus and is required for the synthesis of G and SG RNA. J Biomed Sci 17: 59 [CrossRef] [PubMed].
    [Google Scholar]
  60. Hahn Y.S. , Grakoui A. , Rice C.M. , Strauss E.G. , Strauss J.H. . ( 1989a;). Mapping of RNA temperature-sensitive mutants of Sindbis virus: complementation group F mutants have lesions in nsP4. J Virol 63: 1194–1202 [PubMed].
    [Google Scholar]
  61. Hahn Y.S. , Strauss E.G. , Strauss J.H. . ( 1989b;). Mapping of RNA temperature-sensitive mutants of Sindbis virus: assignment of complementation groups A, B, and G to nonstructural proteins. J Virol 63: 3142–3150 [PubMed].
    [Google Scholar]
  62. Hardy R.W. . ( 2006;). The role of the 3′ terminus of the Sindbis virus genome in minus-strand initiation site selection. Virology 345: 520–531 [CrossRef] [PubMed].
    [Google Scholar]
  63. Hardy R.W. , Rice C.M. . ( 2005;). Requirements at the 3′ end of the sindbis virus genome for efficient synthesis of minus-strand RNA. J Virol 79: 4630–4639 [CrossRef] [PubMed].
    [Google Scholar]
  64. Hardy W.R. , Strauss J.H. . ( 1989;). Processing the nonstructural polyproteins of sindbis virus: nonstructural proteinase is in the C-terminal half of nsP2 and functions both in cis and in trans. J Virol 63: 4653–4664 [PubMed].
    [Google Scholar]
  65. Hardy W.R. , Hahn Y.S. , de Groot R.J. , Strauss E.G. , Strauss J.H. . ( 1990;). Synthesis and processing of the nonstructural polyproteins of several temperature-sensitive mutants of Sindbis virus. Virology 177: 199–208 [CrossRef] [PubMed].
    [Google Scholar]
  66. Hefti E. , Bishop D.H. , Dubin D.T. , Stollar V. . ( 1975;). 5′ Nucleotide sequence of sindbis viral RNA. J Virol 17: 149–159 [PubMed].
    [Google Scholar]
  67. Herold J. , Andino R. . ( 2001;). Poliovirus RNA replication requires genome circularization through a protein-protein bridge. Mol Cell 7: 581–591 [CrossRef] [PubMed].
    [Google Scholar]
  68. Hertz J.M. , Huang H.V. . ( 1992;). Utilization of heterologous alphavirus junction sequences as promoters by Sindbis virus. J Virol 66: 857–864 [PubMed].
    [Google Scholar]
  69. Hill K.R. , Hajjou M. , Hu J.Y. , Raju R. . ( 1997;). RNA–RNA recombination in Sindbis virus: roles of the 3′ conserved motif, poly(A) tail, and nonviral sequences of template RNAs in polymerase recognition and template switching. J Virol 71: 2693–2704 [PubMed].
    [Google Scholar]
  70. Hyde J.L. , Gardner C.L. , Kimura T. , White J.P. , Liu G. , Trobaugh D.W. , Huang C. , Tonelli M. , Paessler S. , other authors . ( 2014;). A viral RNA structural element alters host recognition of nonself RNA. Science 343: 783–787 [CrossRef] [PubMed].
    [Google Scholar]
  71. James F.D. , Hietala K.A. , Eldar D. , Guess T.E. , Cone C. , Mundell N.A. , Barnett J.V. , Raju R. . ( 2007;). Efficient replication, and evolution of Sindbis virus genomes with non-canonical 3′A/U-rich elements (NC3ARE) in neonatal mice. Virus Genes 35: 651–662 [CrossRef] [PubMed].
    [Google Scholar]
  72. Johansson M.A. , Powers A.M. , Pesik N. , Cohen N.J. , Staples J.E. . ( 2014;). Nowcasting the spread of chikungunya virus in the Americas. PLoS One 9: e104915 [CrossRef] [PubMed].
    [Google Scholar]
  73. Kääriäinen L. , Ahola T. . ( 2002;). Functions of alphavirus nonstructural proteins in RNA replication. Prog Nucleic Acid Res Mol Biol 71: 187–222 [CrossRef] [PubMed].
    [Google Scholar]
  74. Kallio K. , Hellström K. , Balistreri G. , Spuul P. , Jokitalo E. , Ahola T. . ( 2013;). Template RNA length determines the size of replication complex spherules for Semliki Forest virus. J Virol 87: 9125–9134 [CrossRef] [PubMed].
    [Google Scholar]
  75. Karo-Astover L. , Sarova O. , Merits A. , Zusinaite E. . ( 2010;). The infection of mammalian and insect cells with SFV bearing nsP1 palmitoylation mutations. Virus Res 153: 277–287 [CrossRef] [PubMed].
    [Google Scholar]
  76. Kim K.H. , Rümenapf T. , Strauss E.G. , Strauss J.H. . ( 2004;). Regulation of Semliki Forest virus RNA replication: a model for the control of alphavirus pathogenesis in invertebrate hosts. Virology 323: 153–163 [CrossRef] [PubMed].
    [Google Scholar]
  77. Kim D.Y. , Firth A.E. , Atasheva S. , Frolova E.I. , Frolov I. . ( 2011;). Conservation of a packaging signal and the viral genome RNA packaging mechanism in alphavirus evolution. J Virol 85: 8022–8036 [CrossRef] [PubMed].
    [Google Scholar]
  78. Kinney R.M. , Chang G.J. , Tsuchiya K.R. , Sneider J.M. , Roehrig J.T. , Woodward T.M. , Trent D.W. . ( 1993;). Attenuation of Venezuelan equine encephalitis virus strain TC-83 is encoded by the 5′-noncoding region and the E2 envelope glycoprotein. J Virol 67: 1269–1277 [PubMed].
    [Google Scholar]
  79. Kuhn R.J. , Hong Z. , Strauss J.H. . ( 1990;). Mutagenesis of the 3′ nontranslated region of Sindbis virus RNA. J Virol 64: 1465–1476 [PubMed].
    [Google Scholar]
  80. Kuhn R.J. , Griffin D.E. , Zhang H. , Niesters H.G. , Strauss J.H. . ( 1992;). Attenuation of Sindbis virus neurovirulence by using defined mutations in nontranslated regions of the genome RNA. J Virol 66: 7121–7127 [PubMed].
    [Google Scholar]
  81. Kujala P. , Ikäheimonen A. , Ehsani N. , Vihinen H. , Auvinen P. , Kääriäinen L. . ( 2001;). Biogenesis of the Semliki Forest virus RNA replication complex. J Virol 75: 3873–3884 [CrossRef] [PubMed].
    [Google Scholar]
  82. Kulasegaran-Shylini R. , Atasheva S. , Gorenstein D.G. , Frolov I. . ( 2009a;). Structural and functional elements of the promoter encoded by the 5′ untranslated region of the Venezuelan equine encephalitis virus genome. J Virol 83: 8327–8339 [CrossRef] [PubMed].
    [Google Scholar]
  83. Kulasegaran-Shylini R. , Thiviyanathan V. , Gorenstein D.G. , Frolov I. . ( 2009b;). The 5′UTR-specific mutation in VEEV TC-83 genome has a strong effect on RNA replication and subgenomic RNA synthesis, but not on translation of the encoded proteins. Virology 387: 211–221 [CrossRef] [PubMed].
    [Google Scholar]
  84. La Linn M. , Gardner J. , Warrilow D. , Darnell G.A. , McMahon C.R. , Field I. , Hyatt A.D. , Slade R.W. , Suhrbier A. . ( 2001;). Arbovirus of marine mammals: a new alphavirus isolated from the elephant seal louse. Lepidophthirus macrorhini. J Virol 75: 4103–4109 [CrossRef] [PubMed].
    [Google Scholar]
  85. Laakkonen P. , Hyvönen M. , Peränen J. , Kääriäinen L. . ( 1994;). Expression of Semliki Forest virus nsP1-specific methyltransferase in insect cells and in Escherichia coli . J Virol 68: 7418–7425 [PubMed].
    [Google Scholar]
  86. Laakkonen P. , Ahola T. , Kääriäinen L. . ( 1996;). The effects of palmitoylation on membrane association of Semliki forest virus RNA capping enzyme. J Biol Chem 271: 28567–28571 [CrossRef] [PubMed].
    [Google Scholar]
  87. Laakkonen P. , Auvinen P. , Kujala P. , Kääriäinen L. . ( 1998;). Alphavirus replicase protein NSP1 induces filopodia and rearrangement of actin filaments. J Virol 72: 10265–10269 [PubMed].
    [Google Scholar]
  88. Lampio A. , Kilpeläinen I. , Pesonen S. , Karhi K. , Auvinen P. , Somerharju P. , Kääriäinen L. . ( 2000;). Membrane binding mechanism of an RNA virus-capping enzyme. J Biol Chem 275: 37853–37859 [CrossRef] [PubMed].
    [Google Scholar]
  89. LaStarza M.W. , Grakoui A. , Rice C.M. . ( 1994a;). Deletion and duplication mutations in the C-terminal nonconserved region of Sindbis virus nsP3: effects on phosphorylation and on virus replication in vertebrate and invertebrate cells. Virology 202: 224–232 [CrossRef] [PubMed].
    [Google Scholar]
  90. LaStarza M.W. , Lemm J.A. , Rice C.M. . ( 1994b;). Genetic analysis of the nsP3 region of Sindbis virus: evidence for roles in minus-strand and subgenomic RNA synthesis. J Virol 68: 5781–5791 [PubMed].
    [Google Scholar]
  91. Lemm J.A. , Rice C.M. . ( 1993;). Assembly of functional Sindbis virus RNA replication complexes: requirement for coexpression of P123 and P34. J Virol 67: 1905–1915 [PubMed].
    [Google Scholar]
  92. Lemm J.A. , Rümenapf T. , Strauss E.G. , Strauss J.H. , Rice C.M. . ( 1994;). Polypeptide requirements for assembly of functional Sindbis virus replication complexes: a model for the temporal regulation of minus- and plus-strand RNA synthesis. EMBO J 13: 2925–2934 [PubMed].
    [Google Scholar]
  93. Lemm J.A. , Bergqvist A. , Read C.M. , Rice C.M. . ( 1998;). Template-dependent initiation of Sindbis virus RNA replication in vitro . J Virol 72: 6546–6553 [PubMed].
    [Google Scholar]
  94. Levinson R.S. , Strauss J.H. , Strauss E.G. . ( 1990;). Complete sequence of the genomic RNA of O'nyong-nyong virus and its use in the construction of alphavirus phylogenetic trees. Virology 175: 110–123 [CrossRef] [PubMed].
    [Google Scholar]
  95. Levis R. , Schlesinger S. , Huang H.V. . ( 1990;). Promoter for Sindbis virus RNA-dependent subgenomic RNA transcription. J Virol 64: 1726–1733 [PubMed].
    [Google Scholar]
  96. Li G. , Rice C.M. . ( 1993;). The signal for translational readthrough of a UGA codon in Sindbis virus RNA involves a single cytidine residue immediately downstream of the termination codon. J Virol 67: 5062–5067 [PubMed].
    [Google Scholar]
  97. Li M.-L. , Stollar V. . ( 2004;). Identification of the amino acid sequence in Sindbis virus nsP4 that binds to the promoter for the synthesis of the subgenomic RNA. Proc Natl Acad Sci U S A 101: 9429–9434 [CrossRef] [PubMed].
    [Google Scholar]
  98. Li M.-L. , Stollar V. . ( 2007;). Distinct sites on the Sindbis virus RNA-dependent RNA polymerase for binding to the promoters for the synthesis of genomic and subgenomic RNA. J Virol 81: 4371–4373 [CrossRef] [PubMed].
    [Google Scholar]
  99. Li G.P. , La Starza M.W. , Hardy W.R. , Strauss J.H. , Rice C.M. . ( 1990;). Phosphorylation of Sindbis virus nsP3 in vivo in vitro . Virology 179: 416–427 [CrossRef] [PubMed].
    [Google Scholar]
  100. Li M.-L. , Wang H. , Stollar V. . ( 2010;). In vitro synthesis of Sindbis virus genomic and subgenomic RNAs: influence of nsP4 mutations and nucleoside triphosphate concentrations. J Virol 84: 2732–2739 [CrossRef] [PubMed].
    [Google Scholar]
  101. Lin J.-Y. , Shih S.-R. , Pan M. , Li C. , Lue C.-F. , Stollar V. , Li M.-L. . ( 2009;). hnRNP A1 interacts with the 5′ untranslated regions of enterovirus 71 and Sindbis virus RNA and is required for viral replication. J Virol 83: 6106–6114 [CrossRef] [PubMed].
    [Google Scholar]
  102. Lulla A. , Lulla V. , Tints K. , Ahola T. , Merits A. . ( 2006;). Molecular determinants of substrate specificity for Semliki Forest virus nonstructural protease. J Virol 80: 5413–5422 [CrossRef] [PubMed].
    [Google Scholar]
  103. Lulla V. , Sawicki D.L. , Sawicki S.G. , Lulla A. , Merits A. , Ahola T. . ( 2008;). Molecular defects caused by temperature-sensitive mutations in Semliki Forest virus nsP1.J Virol 82: 9236–9244 [CrossRef] [PubMed].
    [Google Scholar]
  104. Lulla A. , Lulla V. , Merits A. . ( 2012;). Macromolecular assembly-driven processing of the 2/3 cleavage site in the alphavirus replicase polyprotein. J Virol 86: 553–565 [CrossRef] [PubMed].
    [Google Scholar]
  105. Lulla V. , Karo-Astover L. , Rausalu K. , Merits A. , Lulla A. . ( 2013;). Presentation overrides specificity: probing the plasticity of alphaviral proteolytic activity through mutational analysis. J Virol 87: 10207–10220 [CrossRef] [PubMed].
    [Google Scholar]
  106. Malet H. , Coutard B. , Jamal S. , Dutartre H. , Papageorgiou N. , Neuvonen M. , Ahola T. , Forrester N. , Gould E.A. , other authors . ( 2009;). The crystal structures of Chikungunya and Venezuelan equine encephalitis virus nsP3 macro domains define a conserved adenosine binding pocket. J Virol 83: 6534–6545 [CrossRef] [PubMed].
    [Google Scholar]
  107. Martin J.L. , McMillan F.M. . ( 2002;). SAM (dependent) I AM: the S-adenosylmethionine-dependent methyltransferase fold. Curr Opin Struct Biol 12: 783–793 [CrossRef] [PubMed].
    [Google Scholar]
  108. Martinez M.G. , Snapp E.L. , Perumal G.S. , Macaluso F.P. , Kielian M. . ( 2014;). Imaging the alphavirus exit pathway. J Virol 88: 6922–6933 [CrossRef] [PubMed].
    [Google Scholar]
  109. McInerney G.M. , Kedersha N.L. , Kaufman R.J. , Anderson P. , Liljeström P. . ( 2005;). Importance of eIF2alpha phosphorylation and stress granule assembly in alphavirus translation regulation. Mol Biol Cell 16: 3753–3763 [CrossRef] [PubMed].
    [Google Scholar]
  110. Merits A. , Vasiljeva L. , Ahola T. , Kääriäinen L. , Auvinen P. . ( 2001;). Proteolytic processing of Semliki Forest virus-specific non-structural polyprotein by nsP2 protease. J Gen Virol 82: 765–773 [PubMed].[CrossRef]
    [Google Scholar]
  111. Mi S. , Stollar V. . ( 1990;). Both amino acid changes in nsP1 of Sindbis virusLM21 contribute to and are required for efficient expression of the mutant phenotype. Virology 178: 429–434 [CrossRef] [PubMed].
    [Google Scholar]
  112. Mi S. , Stollar V. . ( 1991;). Expression of Sindbis virus nsP1 and methyltransferase activity in Escherichia coli . Virology 184: 423–427 [CrossRef] [PubMed].
    [Google Scholar]
  113. Michel G. , Petrakova O. , Atasheva S. , Frolov I. . ( 2007;). Adaptation of Venezuelan equine encephalitis virus lacking 51-nt conserved sequence element to replication in mammalian and mosquito cells. Virology 362: 475–487 [CrossRef] [PubMed].
    [Google Scholar]
  114. Nasar F. , Palacios G. , Gorchakov R.V. , Guzman H. , Da Rosa A.P. , Savji N. , Popov V.L. , Sherman M.B. , Lipkin W.I. , other authors . ( 2012;). Eilat virus, a unique alphavirus with host range restricted to insects by RNA replication. Proc Natl Acad Sci U S A 109: 14622–14627 [CrossRef] [PubMed].
    [Google Scholar]
  115. Nasar F. , Haddow A.D. , Tesh R.B. , Weaver S.C. . ( 2014;). Eilat virus displays a narrow mosquito vector range. Parasit Vectors 7: 595 [CrossRef] [PubMed].
    [Google Scholar]
  116. Nasar F. , Gorchakov R.V. , Tesh R.B. , Weaver S.C. . ( 2015;). Eilat virus host range restriction is present at multiple levels of the virus life cycle. J Virol 89: 1404–1418 [CrossRef] [PubMed].
    [Google Scholar]
  117. Neuvonen M. , Kazlauskas A. , Martikainen M. , Hinkkanen A. , Ahola T. , Saksela K. . ( 2011;). SH3 domain-mediated recruitment of host cell amphiphysins by alphavirus nsP3 promotes viral RNA replication. PLoS Pathog 7: e1002383 [CrossRef] [PubMed].
    [Google Scholar]
  118. Nickens D.G. , Hardy R.W. . ( 2008;). Structural and functional analyses of stem-loop 1 of the Sindbis virus genome. Virology 370: 158–172 [CrossRef] [PubMed].
    [Google Scholar]
  119. Niesters H.G. , Strauss J.H. . ( 1990a;). Defined mutations in the 5′ nontranslated sequence of Sindbis virus RNA. J Virol 64: 4162–4168 [PubMed].
    [Google Scholar]
  120. Niesters H.G. , Strauss J.H. . ( 1990b;). Mutagenesis of the conserved 51-nucleotide region of Sindbis virus. J Virol 64: 1639–1647 [PubMed].
    [Google Scholar]
  121. Nikonov A. , Mölder T. , Sikut R. , Kiiver K. , Männik A. , Toots U. , Lulla A. , Lulla V. , Utt A. , other authors . ( 2013;). RIG-I and MDA-5 detection of viral RNA-dependent RNA polymerase activity restricts positive-strand RNA virus replication. PLoS Pathog 9: e1003610 [CrossRef] [PubMed].
    [Google Scholar]
  122. O'Reilly E.K. , Kao C.C. . ( 1998;). Analysis of RNA-dependent RNA polymerase structure and function as guided by known polymerase structures and computer predictions of secondary structure. Virology 252: 287–303 [CrossRef] [PubMed].
    [Google Scholar]
  123. Oberste M.S. , Parker M.D. , Smith J.F. . ( 1996;). Complete sequence of Venezuelan equine encephalitis virus subtype IE reveals conserved and hypervariable domains within the C terminus of nsP3. Virology 219: 314–320 [CrossRef] [PubMed].
    [Google Scholar]
  124. Ou J.H. , Strauss E.G. , Strauss J.H. . ( 1981;). Comparative studies of the 3′-terminal sequences of several alpha virus RNAs. Virology 109: 281–289 [CrossRef] [PubMed].
    [Google Scholar]
  125. Ou J.H. , Rice C.M. , Dalgarno L. , Strauss E.G. , Strauss J.H. . ( 1982a;). Sequence studies of several alphavirus genomic RNAs in the region containing the start of the subgenomic RNA. Proc Natl Acad Sci U S A 79: 5235–5239 [CrossRef] [PubMed].
    [Google Scholar]
  126. Ou J.H. , Trent D.W. , Strauss J.H. . ( 1982b;). The 3′-non-coding regions of alphavirus RNAs contain repeating sequences. J Mol Biol 156: 719–730 [CrossRef] [PubMed].
    [Google Scholar]
  127. Pardigon N. , Strauss J.H. . ( 1992;). Cellular proteins bind to the 3′ end of Sindbis virus minus-strand RNA. J Virol 66: 1007–1015 [PubMed].
    [Google Scholar]
  128. Pardigon N. , Strauss J.H. . ( 1996;). Mosquito homolog of the La autoantigen binds to Sindbis virus RNA. J Virol 70: 1173–1181 [PubMed].
    [Google Scholar]
  129. Park E. , Griffin D.E. . ( 2009;). The nsP3 macro domain is important for Sindbis virus replication in neurons and neurovirulence in mice. Virology 388: 305–314 [CrossRef] [PubMed].
    [Google Scholar]
  130. Pehrson J.R. , Fuji R.N. . ( 1998;). Evolutionary conservation of histone macroH2A subtypes and domains. Nucleic Acids Res 26: 2837–2842 [CrossRef] [PubMed].
    [Google Scholar]
  131. Peränen J. , Takkinen K. , Kalkkinen N. , Kääriäinen L. . ( 1988;). Semliki Forest virus-specific non-structural protein nsP3 is a phosphoprotein. J Gen Virol 69: 2165–2178 [CrossRef] [PubMed].
    [Google Scholar]
  132. Peränen J. , Laakkonen P. , Hyvönen M. , Kääriäinen L. . ( 1995;). The alphavirus replicase protein nsP1 is membrane-associated and has affinity to endocytic organelles. Virology 208: 610–620 [CrossRef] [PubMed].
    [Google Scholar]
  133. Powers A.M. , Brault A.C. , Shirako Y. , Strauss E.G. , Kang W. , Strauss J.H. , Weaver S.C. . ( 2001;). Evolutionary relationships and systematics of the alphaviruses. J Virol 75: 10118–10131 [CrossRef] [PubMed].
    [Google Scholar]
  134. Raju R. , Huang H.V. . ( 1991;). Analysis of Sindbis virus promoter recognition in vivo, using novel vectors with two subgenomic mRNA promoters. J Virol 65: 2501–2510 [PubMed].
    [Google Scholar]
  135. Raju R. , Hajjou M. , Hill K.R. , Botta V. , Botta S. . ( 1999;). In vivo addition of poly(A) tail and AU-rich sequences to the 3′ terminus of the Sindbis virus RNA genome: a novel 3′-end repair pathway. J Virol 73: 2410–2419 [PubMed].
    [Google Scholar]
  136. Reynaud J.M. , Kim D.Y. , Atasheva S. , Rasalouskaya A. , White J.P. , Diamond M.S. , Weaver S.C. , Frolova E.I. , Frolov I. . ( 2015;). IFIT1 differentially interferes with translation and replication of alphavirus genomes and promotes induction of type I interferon. PLoS Pathog 11: e1004863 [CrossRef] [PubMed].
    [Google Scholar]
  137. Rikkonen M. . ( 1996;). Functional significance of the nuclear-targeting and NTP-binding motifs of Semliki Forest virus nonstructural protein nsP2. Virology 218: 352–361 [CrossRef] [PubMed].
    [Google Scholar]
  138. Rikkonen M. , Peränen J. , Kääriäinen L. . ( 1994;). ATPase and GTPase activities associated with Semliki Forest virus nonstructural protein nsP2. J Virol 68: 5804–5810 [PubMed].
    [Google Scholar]
  139. Rozanov M.N. , Koonin E.V. , Gorbalenya A.E. . ( 1992;). Conservation of the putative methyltransferase domain: a hallmark of the ‘Sindbis-like’ supergroup of positive-strand RNA viruses. J Gen Virol 73: 2129–2134 [CrossRef] [PubMed].
    [Google Scholar]
  140. Rubach J.K. , Wasik B.R. , Rupp J.C. , Kuhn R.J. , Hardy R.W. , Smith J.L. . ( 2009;). Characterization of purified Sindbis virus nsP4 RNA-dependent RNA polymerase activity in vitro . Virology 384: 201–208 [CrossRef] [PubMed].
    [Google Scholar]
  141. Rümenapf T. , Strauss E.G. , Strauss J.H. . ( 1994;). Subgenomic mRNA of Aura alphavirus is packaged into virions. J Virol 68: 56–62 [PubMed].
    [Google Scholar]
  142. Rupp J.C. , Jundt N. , Hardy R.W. . ( 2011;). Requirement for the amino-terminal domain of sindbis virus nsP4 during virus infection. J Virol 85: 3449–3460 [CrossRef] [PubMed].
    [Google Scholar]
  143. Russo A.T. , White M.A. , Watowich S.J. . ( 2006;). The crystal structure of the Venezuelan equine encephalitis alphavirus nsP2 protease. Structure 14: 1449–1458 [CrossRef] [PubMed].
    [Google Scholar]
  144. Salonen A. , Vasiljeva L. , Merits A. , Magden J. , Jokitalo E. , Kääriäinen L. . ( 2003;). Properly folded nonstructural polyprotein directs the semliki forest virus replication complex to the endosomal compartment. J Virol 77: 1691–1702 [CrossRef] [PubMed].
    [Google Scholar]
  145. Salonen A. , Ahola T. , Kääriäinen L. . ( 2005;). Viral RNA replication in association with cellular membranes. Curr Top Microbiol Immunol 285: 139–173 [PubMed].
    [Google Scholar]
  146. Sawicki D.L. , Gomatos P.J. . ( 1976;). Replication of semliki forest virus: polyadenylate in plus-strand RNA and polyuridylate in minus-strand RNA. J Virol 20: 446–464 [PubMed].
    [Google Scholar]
  147. Sawicki D.L. , Sawicki S.G. . ( 1980;). Short-lived minus-strand polymerase for Semliki Forest virus. J Virol 34: 108–118 [PubMed].
    [Google Scholar]
  148. Sawicki D.L. , Sawicki S.G. . ( 1985;). Functional analysis of the A complementation group mutants of Sindbis HR virus. Virology 144: 20–34 [CrossRef] [PubMed].
    [Google Scholar]
  149. Sawicki D.L. , Sawicki S.G. . ( 1993;). A second nonstructural protein functions in the regulation of alphavirus negative-strand RNA synthesis. J Virol 67: 3605–3610 [PubMed].
    [Google Scholar]
  150. Sawicki D.L. , Sawicki S.G. . ( 1994;). Alphavirus positive and negative strand RNA synthesis and the role of polyproteins in formation of viral replication complexes. Arch Virol Suppl 9: 393–405 [PubMed].
    [Google Scholar]
  151. Sawicki D.L. , Kääriäinen L. , Lambek C. , Gomatos P.J. . ( 1978;). Mechanism for control of synthesis of Semliki Forest virus 26S and 42S RNA. J Virol 25: 19–27 [PubMed].
    [Google Scholar]
  152. Sawicki D.L. , Silverman R.H. , Williams B.R. , Sawicki S.G. . ( 2003;). Alphavirus minus-strand synthesis and persistence in mouse embryo fibroblasts derived from mice lacking RNase L and protein kinase R. J Virol 77: 1801–1811 [CrossRef] [PubMed].
    [Google Scholar]
  153. Sawicki D.L. , Perri S. , Polo J.M. , Sawicki S.G. . ( 2006;). Role for nsP2 proteins in the cessation of alphavirus minus-strand synthesis by host cells. J Virol 80: 360–371 [CrossRef] [PubMed].
    [Google Scholar]
  154. Saxton-Shaw K.D. , Ledermann J.P. , Borland E.M. , Stovall J.L. , Mossel E.C. , Singh A.J. , Wilusz J. , Powers A.M. . ( 2013;). O'nyong nyong virus molecular determinants of unique vector specificity reside in non-structural protein 3. PLoS Negl Trop Dis 7: e1931 [CrossRef] [PubMed].
    [Google Scholar]
  155. Schechter I. , Berger A. . ( 1967;). On the size of the active site in proteases. I. Papain. Biochem Biophys Res Commun 27: 157–162 [CrossRef] [PubMed].
    [Google Scholar]
  156. Scheidel L.M. , Stollar V. . ( 1991;). Mutations that confer resistance to mycophenolic acid and ribavirin on Sindbis virus map to the nonstructural protein nsP1. Virology 181: 490–499 [CrossRef] [PubMed].
    [Google Scholar]
  157. Schluckebier G. , O'Gara M. , Saenger W. , Cheng X. . ( 1995;). Universal catalytic domain structure of AdoMet-dependent methyltransferases. J Mol Biol 247: 16–20 [CrossRef] [PubMed].
    [Google Scholar]
  158. Scholte F.E. , Tas A. , Albulescu I.C. , Zˇusinaite E. , Merits A. , Snijder E.J. , van Hemert M.J. . ( 2015;). Stress granule components G3BP1 and G3BP2 play a proviral role early in Chikungunya virus replication. J Virol 89: 4457–4469 [PubMed].[CrossRef]
    [Google Scholar]
  159. Shin G. , Yost S.A. , Miller M.T. , Elrod E.J. , Grakoui A. , Marcotrigiano J. . ( 2012;). Structural and functional insights into alphavirus polyprotein processing and pathogenesis. Proc Natl Acad Sci U S A 109: 16534–16539 [CrossRef] [PubMed].
    [Google Scholar]
  160. Shirako Y. , Strauss J.H. . ( 1990;). Cleavage between nsP1 and nsP2 initiates the processing pathway of Sindbis virus nonstructural polyprotein P123. Virology 177: 54–64 [CrossRef] [PubMed].
    [Google Scholar]
  161. Shirako Y. , Strauss J.H. . ( 1994;). Regulation of Sindbis virus RNA replication: uncleaved P123 and nsP4 function in minus-strand RNA synthesis, whereas cleaved products from P123 are required for efficient plus-strand RNA synthesis. J Virol 68: 1874–1885 [PubMed].
    [Google Scholar]
  162. Shirako Y. , Strauss J.H. . ( 1998;). Requirement for an aromatic amino acid or histidine at the N terminus of Sindbis virus RNA polymerase. J Virol 72: 2310–2315 [PubMed].
    [Google Scholar]
  163. Shirako Y. , Strauss E.G. , Strauss J.H. . ( 2003;). Modification of the 5′ terminus of Sindbis virus genomic RNA allows nsP4 RNA polymerases with nonaromatic amino acids at the N terminus to function in RNA replication. J Virol 77: 2301–2309 [CrossRef] [PubMed].
    [Google Scholar]
  164. Simmons D.T. , Strauss J.H. . ( 1972a;). Replication of Sindbis virus. I. Relative size and genetic content of 26 s and 49 s RNA. J Mol Biol 71: 599–613 [CrossRef] [PubMed].
    [Google Scholar]
  165. Simmons D.T. , Strauss J.H. . ( 1972b;). Replication of Sindbis virus. II. Multiple forms of double-stranded RNA isolated from infected cells. J Mol Biol 71: 615–631 [PubMed].[CrossRef]
    [Google Scholar]
  166. Sokoloski K.J. , Dickson A.M. , Chaskey E.L. , Garneau N.L. , Wilusz C.J. , Wilusz J. . ( 2010;). Sindbis virus usurps the cellular HuR protein to stabilize its transcripts and promote productive infections in mammalian and mosquito cells. Cell Host Microbe 8: 196–207 [CrossRef] [PubMed].
    [Google Scholar]
  167. Sokoloski K.J. , Haist K.C. , Morrison T.E. , Mukhopadhyay S. , Hardy R.W. . ( 2015;). Noncapped alphavirus genomic RNAs and their role during infection. J Virol 89: 6080–6092 [CrossRef] [PubMed].
    [Google Scholar]
  168. Spuul P. , Salonen A. , Merits A. , Jokitalo E. , Kääriäinen L. , Ahola T. . ( 2007;). Role of the amphipathic peptide of Semliki forest virus replicase protein nsP1 in membrane association and virus replication. J Virol 81: 872–883 [CrossRef] [PubMed].
    [Google Scholar]
  169. Spuul P. , Balistreri G. , Kääriäinen L. , Ahola T. . ( 2010;). Phosphatidylinositol 3-kinase-, actin-, and microtubule-dependent transport of Semliki Forest Virus replication complexes from the plasma membrane to modified lysosomes. J Virol 84: 7543–7557 [CrossRef] [PubMed].
    [Google Scholar]
  170. Spuul P. , Balistreri G. , Hellström K. , Golubtsov A.V. , Jokitalo E. , Ahola T. . ( 2011;). Assembly of alphavirus replication complexes from RNA and protein components in a novel trans-replication system in mammalian cells. J Virol 85: 4739–4751 [CrossRef] [PubMed].
    [Google Scholar]
  171. Stoermer Burrack K.A. , Hawman D.W. , Jupille H.J. , Oko L. , Minor M. , Shives K.D. , Gunn B.M. , Long K.M. , Morrison T.E. . ( 2014;). Attenuating mutations in nsP1 reveal tissue-specific mechanisms for control of Ross River virus infection. J Virol 88: 3719–3732 [CrossRef] [PubMed].
    [Google Scholar]
  172. Strauss J.H. , Strauss E.G. . ( 1994;). The alphaviruses: gene expression, replication, and evolution. Microbiol Rev 58: 491–562 [PubMed].
    [Google Scholar]
  173. Strauss E.G. , Rice C.M. , Strauss J.H. . ( 1983;). Sequence coding for the alphavirus nonstructural proteins is interrupted by an opal termination codon. Proc Natl Acad Sci U S A 80: 5271–5275 [CrossRef] [PubMed].
    [Google Scholar]
  174. Strauss E.G. , Rice C.M. , Strauss J.H. . ( 1984;). Complete nucleotide sequence of the genomic RNA of Sindbis virus. Virology 133: 92–110 [CrossRef] [PubMed].
    [Google Scholar]
  175. Suopanki J. , Sawicki D.L. , Sawicki S.G. , Kääriäinen L. . ( 1998;). Regulation of alphavirus 26S mRNA transcription by replicase component nsP2. J Gen Virol 79: 309–319 [PubMed].[CrossRef]
    [Google Scholar]
  176. Tomar S. , Hardy R.W. , Smith J.L. , Kuhn R.J. . ( 2006;). Catalytic core of alphavirus nonstructural protein nsP4 possesses terminal adenylyltransferase activity. J Virol 80: 9962–9969 [CrossRef] [PubMed].
    [Google Scholar]
  177. Tomar S. , Narwal M. , Harms E. , Smith J.L. , Kuhn R.J. . ( 2011;). Heterologous production, purification and characterization of enzymatically active Sindbis virus nonstructural protein nsP1. Protein Expr Purif 79: 277–284 [CrossRef] [PubMed].
    [Google Scholar]
  178. Tuittila M. , Hinkkanen A.E. . ( 2003;). Amino acid mutations in the replicase protein nsP3 of Semliki Forest virus cumulatively affect neurovirulence. J Gen Virol 84: 1525–1533 [CrossRef] [PubMed].
    [Google Scholar]
  179. Tuittila M.T. , Santagati M.G. , Röyttä M. , Määttä J.A. , Hinkkanen A.E. . ( 2000;). Replicase complex genes of Semliki Forest virus confer lethal neurovirulence. J Virol 74: 4579–4589 [CrossRef] [PubMed].
    [Google Scholar]
  180. Varjak M. , Saul S. , Arike L. , Lulla A. , Peil L. , Merits A. . ( 2013;). Magnetic fractionation and proteomic dissection of cellular organelles occupied by the late replication complexes of Semliki Forest virus. J Virol 87: 10295–10312 [CrossRef] [PubMed].
    [Google Scholar]
  181. Vasiljeva L. , Merits A. , Auvinen P. , Kääriäinen L. . ( 2000;). Identification of a novel function of the alphavirus capping apparatus. RNA 5′-triphosphatase activity of Nsp2.J Biol Chem 275: 17281–17287 [CrossRef] [PubMed].
    [Google Scholar]
  182. Vasiljeva L. , Merits A. , Golubtsov A. , Sizemskaja V. , Kääriäinen L. , Ahola T. . ( 2003;). Regulation of the sequential processing of Semliki Forest virus replicase polyprotein. J Biol Chem 278: 41636–41645 [CrossRef] [PubMed].
    [Google Scholar]
  183. Ventoso I. , Sanz M.A. , Molina S. , Berlanga J.J. , Carrasco L. , Esteban M. . ( 2006;). Translational resistance of late alphavirus mRNA to eIF2alpha phosphorylation: a strategy to overcome the antiviral effect of protein kinase PKR. Genes Dev 20: 87–100 [CrossRef] [PubMed].
    [Google Scholar]
  184. Vihinen H. , Ahola T. , Tuittila M. , Merits A. , Kääriäinen L. . ( 2001;). Elimination of phosphorylation sites of Semliki Forest virus replicase protein nsP3. J Biol Chem 276: 5745–5752 [CrossRef] [PubMed].
    [Google Scholar]
  185. Villoing S. , Béarzotti M. , Chilmonczyk S. , Castric J. , Brémont M. . ( 2000;). Rainbow trout sleeping disease virus is an atypical alphavirus. J Virol 74: 173–183 [CrossRef] [PubMed].
    [Google Scholar]
  186. Wang Y.F. , Sawicki S.G. , Sawicki D.L. . ( 1991;). Sindbis virus nsP1 functions in negative-strand RNA synthesis. J Virol 65: 985–988 [PubMed].
    [Google Scholar]
  187. Wang Y.F. , Sawicki S.G. , Sawicki D.L. . ( 1994;). Alphavirus nsP3 functions to form replication complexes transcribing negative-strand RNA. J Virol 68: 6466–6475 [PubMed].
    [Google Scholar]
  188. Wang H.L. , O'Rear J. , Stollar V. . ( 1996;). Mutagenesis of the Sindbis virus nsP1 protein: effects on methyltransferase activity and viral infectivity. Virology 217: 527–531 [CrossRef] [PubMed].
    [Google Scholar]
  189. Weaver S.C. . ( 2014;). Arrival of chikungunya virus in the new world: prospects for spread and impact on public health. PLoS Negl Trop Dis 8: e2921 [CrossRef] [PubMed].
    [Google Scholar]
  190. Weaver S.C. , Lecuit M. . ( 2015;). Chikungunya virus and the global spread of a mosquito-borne disease. N Engl J Med 372: 1231–1239 [CrossRef] [PubMed].
    [Google Scholar]
  191. Weiss B. , Nitschko H. , Ghattas I. , Wright R. , Schlesinger S. . ( 1989;). Evidence for specificity in the encapsidation of Sindbis virus RNAs. J Virol 63: 5310–5318 [PubMed].
    [Google Scholar]
  192. Weiss B. , Geigenmüller-Gnirke U. , Schlesinger S. . ( 1994;). Interactions between Sindbis virus RNAs and a 68 amino acid derivative of the viral capsid protein further defines the capsid binding site. Nucleic Acids Res 22: 780–786 [CrossRef] [PubMed].
    [Google Scholar]
  193. Weston J.H. , Welsh M.D. , McLoughlin M.F. , Todd D. . ( 1999;). Salmon pancreas disease virus, an alphavirus infecting farmed Atlantic salmon, Salmo salar L. Virology 256: 188–195 [CrossRef] [PubMed].
    [Google Scholar]
  194. Wielgosz M.M. , Huang H.V. . ( 1997;). A novel viral RNA species in Sindbis virus-infected cells. J Virol 71: 9108–9117 [PubMed].
    [Google Scholar]
  195. Wielgosz M.M. , Raju R. , Huang H.V. . ( 2001;). Sequence requirements for Sindbis virus subgenomic mRNA promoter function in cultured cells. J Virol 75: 3509–3519 [CrossRef] [PubMed].
    [Google Scholar]
  196. You S. , Padmanabhan R. . ( 1999;). A novel in vitro replication system for Dengue virus. Initiation of RNA synthesis at the 3′-end of exogenous viral RNA templates requires 5′- and 3′-terminal complementary sequence motifs of the viral RNA. J Biol Chem 274: 33714–33722 [CrossRef] [PubMed].
    [Google Scholar]
  197. Zhang W. , Mukhopadhyay S. , Pletnev S.V. , Baker T.S. , Kuhn R.J. , Rossmann M.G. . ( 2002;). Placement of the structural proteins in Sindbis virus. J Virol 76: 11645–11658 [CrossRef] [PubMed].
    [Google Scholar]
  198. Zhang D. , Tözsér J. , Waugh D.S. . ( 2009;). Molecular cloning, overproduction, purification and biochemical characterization of the p39 nsp2 protease domains encoded by three alphaviruses. Protein Expr Purif 64: 89–97 [CrossRef] [PubMed].
    [Google Scholar]
  199. Zusinaite E. , Tints K. , Kiiver K. , Spuul P. , Karo-Astover L. , Merits A. , Sarand I. . ( 2007;). Mutations at the palmitoylation site of non-structural protein nsP1 of Semliki Forest virus attenuate virus replication and cause accumulation of compensatory mutations. J Gen Virol 88: 1977–1985 [CrossRef] [PubMed].
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/jgv.0.000249
Loading
/content/journal/jgv/10.1099/jgv.0.000249
Loading

Data & Media loading...

Most cited articles

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error