1. EigenM (1993) Viral quasispecies. Sci Am 269: 42–49.
2. DrakeJW, HollandJJ (1999) Mutation rates among RNA viruses. Proc Natl Acad Sci U S A 96: 13910–13913.
3. HollandJJ, De La TorreJC, SteinhauerDA (1992) RNA virus populations as quasispecies. Curr Top Microbiol Immunol 176: 1–20.
4. LauringAS, AndinoR (2010) Quasispecies theory and the behavior of RNA viruses. PLoS Pathog 6: e1001005.
5. PfeifferJK, KirkegaardK (2003) A single mutation in poliovirus RNA-dependent RNA polymerase confers resistance to mutagenic nucleotide analogs via increased fidelity. Proc Natl Acad Sci U S A 100: 7289–7294.
6. GnadigNF, BeaucourtS, CampagnolaG, BorderiaAV, Sanz-RamosM, et al. (2012) Coxsackievirus B3 mutator strains are attenuated in vivo. Proc Natl Acad Sci U S A 109: E2294–2303.
7. GrahamRL, BeckerMM, EckerleLD, BollesM, DenisonMR, et al. (2012) A live, impaired-fidelity coronavirus vaccine protects in an aged, immunocompromised mouse model of lethal disease. Nat Med 18: 1820–1826.
8. ArnoldJJ, VignuzziM, StoneJK, AndinoR, CameronCE (2005) Remote site control of an active site fidelity checkpoint in a viral RNA-dependent RNA polymerase. J Biol Chem 280: 25706–25716.
9. Ferrer-OrtaC, SierraM, AgudoR, de la HigueraI, AriasA, et al. (2010) Structure of foot-and-mouth disease virus mutant polymerases with reduced sensitivity to ribavirin. J Virol 84: 6188–6199.
10. ManskyLM, CunninghamKS (2000) Virus mutators and antimutators: roles in evolution, pathogenesis and emergence. Trends Genet 16: 512–517.
11. SpeyerJF (1965) Mutagenic DNA polymerase. Biochem Biophys Res Commun 21: 6–8.
12. DrakeJW, AllenEF, ForsbergSA, PreparataRM, GreeningEO (1969) Genetic control of mutation rates in bacteriophageT4. Nature 221: 1128–1132.
13. SuarezP, ValcarcelJ, OrtinJ (1992) Heterogeneity of the mutation rates of influenza A viruses: isolation of mutator mutants. J Virol 66: 2491–2494.
14. SadeghipourS, BekEJ, McMinnPC (2013) Ribavirin-resistant mutants of human enterovirus 71 express a high replication fidelity phenotype during growth in cell culture. J Virol 87: 1759–1769.
15. FurioV, MoyaA, SanjuanR (2007) The cost of replication fidelity in human immunodeficiency virus type 1. Proc Biol Sci 274: 225–230.
16. FurioV, MoyaA, SanjuanR (2005) The cost of replication fidelity in an RNA virus. Proc Natl Acad Sci U S A 102: 10233–10237.
17. WeeksSA, LeeCA, ZhaoY, SmidanskyED, AugustA, et al. (2012) A Polymerase mechanism-based strategy for viral attenuation and vaccine development. J Biol Chem 287: 31618–31622.
18. GongP, PeersenOB (2010) Structural basis for active site closure by the poliovirus RNA-dependent RNA polymerase. Proc Natl Acad Sci U S A 107: 22505–22510.
19. VignuzziM, StoneJK, ArnoldJJ, CameronCE, AndinoR (2006) Quasispecies diversity determines pathogenesis through cooperative interactions in a viral population. Nature 439: 344–348.
20. HolmesEC (2003) Error thresholds and the constraints to RNA virus evolution. Trends Microbiol 11: 543–546.
21. Holland EDaJJ (1994) Mutation rates and rapid evolution of RNA viruses. In: Morse SS, editor. The Evolutionary Biology of Viruses. New York: Raven Press. pp. 161–184.
22. HollandJJ, DomingoE, de la TorreJC, SteinhauerDA (1990) Mutation frequencies at defined single codon sites in vesicular stomatitis virus and poliovirus can be increased only slightly by chemical mutagenesis. J Virol 64: 3960–3962.
23. LoebLA, EssigmannJM, KazaziF, ZhangJ, RoseKD, et al. (1999) Lethal mutagenesis of HIV with mutagenic nucleoside analogs. Proc Natl Acad Sci U S A 96: 1492–1497.
24. PfeifferJK, KirkegaardK (2005) Increased fidelity reduces poliovirus fitness and virulence under selective pressure in mice. PLoS Pathog 1: e11.
25. CoffeyLL, BeeharryY, BorderiaAV, BlancH, VignuzziM (2011) Arbovirus high fidelity variant loses fitness in mosquitoes and mice. Proc Natl Acad Sci U S A 108: 16038–16043.
26. SchultzU, FitchWM, LudwigS, MandlerJ, ScholtissekC (1991) Evolution of pig influenza viruses. Virology 183: 61–73.
27. VignuzziM, StoneJK, AndinoR (2005) Ribavirin and lethal mutagenesis of poliovirus: molecular mechanisms, resistance and biological implications. Virus Res 107: 173–181.
28. AndersonJP, DaifukuR, LoebLA (2004) Viral error catastrophe by mutagenic nucleosides. Annu Rev Microbiol 58: 183–205.
29. BullJJ, SanjuanR, WilkeCO (2007) Theory of lethal mutagenesis for viruses. J Virol 81: 2930–2939.
30. GraciJD, CameronCE (2008) Therapeutically targeting RNA viruses via lethal mutagenesis. Future Virol 3: 553–566.
31. DappMJ, PattersonSE, ManskyLM (2012) Back to the future: revisiting HIV-1 lethal mutagenesis. Trends Microbiol 21: 56–62.
32. DappMJ, HeinemanRH, ManskyLM (2013) Interrelationship between HIV-1 fitness and mutation rate. J Mol Biol 425: 41–53.
33. CoffeyLL, VignuzziM (2011) Host alternation of chikungunya virus increases fitness while restricting population diversity and adaptability to novel selective pressures. J Virol 85: 1025–1035.
34. CoffeyLL, ForresterN, TsetsarkinK, VasilakisN, WeaverSC (2013) Factors shaping the adaptive landscape for arboviruses: implications for the emergence of disease. Future Microbiol 8: 155–176.
35. CoffeyLL, VasilakisN, BraultAC, PowersAM, TripetF, et al. (2008) Arbovirus evolution in vivo is constrained by host alternation. Proc Natl Acad Sci U S A 105: 6970–6975.
36. CiotaAT, LovelaceAO, JiaY, DavisLJ, YoungDS, et al. (2008) Characterization of mosquito-adapted West Nile virus. J Gen Virol 89: 1633–1642.
37. GreeneIP, WangE, DeardorffER, MilleronR, DomingoE, et al. (2005) Effect of alternating passage on adaptation of sindbis virus to vertebrate and invertebrate cells. J Virol 79: 14253–14260.
38. DeardorffER, FitzpatrickKA, JerzakGV, ShiPY, KramerLD, et al. (2011) West Nile virus experimental evolution in vivo and the trade-off hypothesis. PLoS Pathog 7: e1002335.
39. ForresterNL, GuerboisM, SeymourRL, SprattH, WeaverSC (2012) Vector-borne transmission imposes a severe bottleneck on an RNA virus population. PLoS Pathog 8: e1002897.
40. WeaverSC, Rico-HesseR, ScottTW (1992) Genetic diversity and slow rates of evolution in New World alphaviruses. Curr Top Microbiol Immunol 176: 99–117.
41. CiotaAT, NgoKA, LovelaceAO, PayneAF, ZhouY, et al. (2007) Role of the mutant spectrum in adaptation and replication of West Nile virus. J Gen Virol 88: 865–874.
42. LinSR, HsiehSC, YuehYY, LinTH, ChaoDY, et al. (2004) Study of sequence variation of dengue type 3 virus in naturally infected mosquitoes and human hosts: implications for transmission and evolution. J Virol 78: 12717–12721.
43. JerzakG, BernardKA, KramerLD, EbelGD (2005) Genetic variation in West Nile virus from naturally infected mosquitoes and birds suggests quasispecies structure and strong purifying selection. J Gen Virol 86: 2175–2183.
44. KurosuT (2011) Quasispecies of dengue virus. Trop Med Health 39: 29–36.
45. CiotaAT, EhrbarDJ, Van SlykeGA, WillseyGG, KramerLD (2012) Cooperative interactions in the West Nile virus mutant swarm. BMC Evol Biol 12: 58.
46. KarpeYA, AherPP, LoleKS (2011) NTPase and 5′-RNA triphosphatase activities of Chikungunya virus nsP2 protein. PLoS One 6: e22336.
47. RathoreAP, NgML, VasudevanSG (2013) Differential unfolded protein response during Chikungunya and Sindbis virus infection: CHIKV nsP4 suppresses eIF2alpha phosphorylation. Virol J 10: 36.
48. MaletH, CoutardB, JamalS, DutartreH, PapageorgiouN, et al. (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.
49. FrosJJ, DomeradzkaNE, BaggenJ, GeertsemaC, FlipseJ, et al. (2012) Chikungunya virus nsP3 blocks stress granule assembly by recruitment of G3BP into cytoplasmic foci. J Virol 86: 10873–10879.
50. JonesPH, MaricM, MadisonMN, MauryW, RollerRJ, et al. (2013) BST-2/tetherin-mediated restriction of chikungunya (CHIKV) VLP budding is counteracted by CHIKV non-structural protein 1 (nsP1). Virology 438: 37–49.
51. SchwartzO, AlbertML (2010) Biology and pathogenesis of chikungunya virus. Nat Rev Microbiol 8: 491–500.
52. SolignatM, GayB, HiggsS, BriantL, DevauxC (2009) Replication cycle of chikungunya: a re-emerging arbovirus. Virology 393: 183–197.
53. Mayuri, GedersTW, SmithJL, KuhnRJ (2008) Role for conserved residues of sindbis virus nonstructural protein 2 methyltransferase-like domain in regulation of minus-strand synthesis and development of cytopathic infection. J Virol 82: 7284–7297.
54. LemmJA, RiceCM (1993) Roles of nonstructural polyproteins and cleavage products in regulating Sindbis virus RNA replication and transcription. J Virol 67: 1916–1926.
55. Saxton-ShawKD, LedermannJP, BorlandEM, StovallJL, MosselEC, et al. (2013) O'nyong nyong Virus Molecular Determinants of Unique Vector Specificity Reside in Non-Structural Protein 3. PLoS Negl Trop Dis 7: e1931.
56. KimDY, FirthAE, AtashevaS, FrolovaEI, FrolovI (2011) Conservation of a packaging signal and the viral genome RNA packaging mechanism in alphavirus evolution. J Virol 85: 8022–8036.
57. TomarS, HardyRW, SmithJL, KuhnRJ (2006) Catalytic core of alphavirus nonstructural protein nsP4 possesses terminal adenylyltransferase activity. J Virol 80: 9962–9969.
58. CrottyS, MaagD, ArnoldJJ, ZhongW, LauJY, et al. (2000) The broad-spectrum antiviral ribonucleoside ribavirin is an RNA virus mutagen. Nat Med 6: 1375–1379.
59. CameronCE, CastroC (2001) The mechanism of action of ribavirin: lethal mutagenesis of RNA virus genomes mediated by the viral RNA-dependent RNA polymerase. Curr Opin Infect Dis 14: 757–764.
60. McKnightKL, SimpsonDA, LinSC, KnottTA, PoloJM, et al. (1996) Deduced consensus sequence of Sindbis virus strain AR339: mutations contained in laboratory strains which affect cell culture and in vivo phenotypes. J Virol 70: 1981–1989.
61. BeaucourtS, BorderiaAV, CoffeyLL, GnadigNF, Sanz-RamosM, et al. (2011) Isolation of fidelity variants of RNA viruses and characterization of virus mutation frequency. J Vis Exp (52) e2953.
62. Aronesty E (2011) Command-line tools for processing biological sequencing data. Available: http://code.google.com/p/ea-utils/. Accessed 13 December 2013.
63. LiH, DurbinR (2009) Fast and accurate short read alignment with Burrows-Wheeler transform. Bioinformatics 25: 1754–1760.
64. LiH, HandsakerB, WysokerA, FennellT, RuanJ, et al. (2009) The Sequence Alignment/Map format and SAMtools. Bioinformatics 25: 2078–2079.
65. LiK, VenterE, YoosephS, StockwellTB, EckerleLD, et al. (2010) ANDES: Statistical tools for the ANalyses of DEep Sequencing. BMC Res Notes 3: 199.
66. PalP, DowdKA, BrienJD, EdelingMA, GorlatovS, et al. (2013) Development of a highly protective combination monoclonal antibody therapy against Chikungunya virus. PLoS Pathog 9: e1003312.
67. LanciottiRS, KosoyOL, LavenJJ, PanellaAJ, VelezJO, et al. (2007) Chikungunya virus in US travelers returning from India, 2006. Emerg Infect Dis 13: 764–767.
68. PowersAM, LogueCH (2007) Changing patterns of chikungunya virus: re-emergence of a zoonotic arbovirus. J Gen Virol 88: 2363–2377.
69. CherryS, PerrimonN (2004) Entry is a rate-limiting step for viral infection in a Drosophila melanogaster model of pathogenesis. Nat Immunol 5: 81–87.
70. DenisonMR, GrahamRL, DonaldsonEF, EckerleLD, BaricRS (2011) Coronaviruses: an RNA proofreading machine regulates replication fidelity and diversity. RNA Biol 8: 270–279.
71. VignuzziM, WendtE, AndinoR (2008) Engineering attenuated virus vaccines by controlling replication fidelity. Nat Med 14: 154–161.
72. AriasA, ArnoldJJ, SierraM, SmidanskyED, DomingoE, et al. (2008) Determinants of RNA-dependent RNA polymerase (in)fidelity revealed by kinetic analysis of the polymerase encoded by a foot-and-mouth disease virus mutant with reduced sensitivity to ribavirin. J Virol 82: 12346–12355.
73. KorneevaVS, CameronCE (2007) Structure-function relationships of the viral RNA-dependent RNA polymerase: fidelity, replication speed, and initiation mechanism determined by a residue in the ribose-binding pocket. J Biol Chem 282: 16135–16145.
74. CrottyS, CameronCE, AndinoR (2001) RNA virus error catastrophe: direct molecular test by using ribavirin. Proc Natl Acad Sci U S A 98: 6895–6900.
75. VasilakisN, DeardorffER, KenneyJL, RossiSL, HanleyKA, et al. (2009) Mosquitoes put the brake on arbovirus evolution: experimental evolution reveals slower mutation accumulation in mosquito than vertebrate cells. PLoS Pathog 5: e1000467.
76. JerzakGV, BernardK, KramerLD, ShiPY, EbelGD (2007) The West Nile virus mutant spectrum is host-dependant and a determinant of mortality in mice. Virology 360: 469–476.
77. JerzakGV, BrownI, ShiPY, KramerLD, EbelGD (2008) Genetic diversity and purifying selection in West Nile virus populations are maintained during host switching. Virology 374: 256–260.
78. BertolottiL, KitronUD, WalkerED, RuizMO, BrawnJD, et al. (2008) Fine-scale genetic variation and evolution of West Nile Virus in a transmission “hot spot” in suburban Chicago, USA. Virology 374: 381–389.
79. CiotaAT, LovelaceAO, JonesSA, PayneA, KramerLD (2007) Adaptation of two flaviviruses results in differences in genetic heterogeneity and virus adaptability. J Gen Virol 88: 2398–2406.
80. BrackneyDE, PeskoKN, BrownIK, DeardorffER, KawatachiJ, et al. (2011) West Nile virus genetic diversity is maintained during transmission by Culex pipiens quinquefasciatus mosquitoes. PLoS One 6: e24466.
81. RosePP, HannaSL, SpiridigliozziA, WannissornN, BeitingDP, et al. (2011) Natural resistance-associated macrophage protein is a cellular receptor for sindbis virus in both insect and mammalian hosts. Cell Host Microbe 10: 97–104.
82. MerklingSH, van RijRP (2013) Beyond RNAi: antiviral defense strategies in Drosophila and mosquito. J Insect Physiol 59: 159–170.
83. SanjuanR, NebotMR, ChiricoN, ManskyLM, BelshawR (2010) Viral mutation rates. J Virol 84: 9733–9748.
84. CastroC, ArnoldJJ, CameronCE (2005) Incorporation fidelity of the viral RNA-dependent RNA polymerase: a kinetic, thermodynamic and structural perspective. Virus Res 107: 141–149.
85. ArnoldJJ, GhoshSK, CameronCE (1999) Poliovirus RNA-dependent RNA polymerase (3D(pol)). Divalent cation modulation of primer, template, and nucleotide selection. J Biol Chem 274: 37060–37069.
86. FreistadtMS, VaccaroJA, EberleKE (2007) Biochemical characterization of the fidelity of poliovirus RNA-dependent RNA polymerase. Virol J 4: 44.
87. LeviLI, GnadigNF, BeaucourtS, McPhersonMJ, BaronB, et al. (2010) Fidelity variants of RNA dependent RNA polymerases uncover an indirect, mutagenic activity of amiloride compounds. PLoS Pathog 6: e1001163.
88. KlimstraWB, RymanKD, JohnstonRE (1998) Adaptation of Sindbis virus to BHK cells selects for use of heparan sulfate as an attachment receptor. J Virol 72: 7357–7366.
89. BernardKA, KlimstraWB, JohnstonRE (2000) Mutations in the E2 glycoprotein of Venezuelan equine encephalitis virus confer heparan sulfate interaction, low morbidity, and rapid clearance from blood of mice. Virology 276: 93–103.
90. BrackneyDE, BeaneJE, EbelGD (2009) RNAi targeting of West Nile virus in mosquito midguts promotes virus diversification. PLoS Pathog 5: e1000502.
91. TeoTH, LumFM, LeeWW, NgLF (2012) Mouse models for Chikungunya virus: deciphering immune mechanisms responsible for disease and pathology. Immunol Res 53: 136–147.
92. CiotaAT, JiaY, PayneAF, JerzakG, DavisLJ, et al. (2009) Experimental passage of St. Louis encephalitis virus in vivo in mosquitoes and chickens reveals evolutionarily significant virus characteristics. PLoS One 4: e7876.
93. PeskoKN, EbelGD (2012) West Nile virus population genetics and evolution. Infect Genet Evol 12: 181–190.
94. EisenbergD, WeissRM, TerwilligerTC, WilcoxW (1982) Hydrophobic Moments and Protein-Structure. Faraday Symposia of the Chemical Society 17: 109–120.