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Sequence-Specific Fidelity Alterations Associated with West Nile Virus Attenuation in Mosquitoes


West Nile virus (WNV) is the most geographically widespread arthropod-borne virus (arbovirus) in the world. Like most arboviruses, WNV is a RNA virus which is highly mutable and exists in nature as genetically diverse mutant swarms. Although many recent studies have investigated the relationship between virus mutation rate and viral fitness, this had not previously been determined for WNV or other flaviviruses. We identified WNV mutations associated with variation in mutation rate using cell culture passage in the presence of a mutagen and engineered these mutations into an infectious WNV clone in order to investigate the causes and consequences of altered fidelity. Our results demonstrate that interactions among proteins which comprise the WNV replication complex can significantly alter both the extent and types of mutations that occur. In addition, we show that both increasing and decreasing WNV fidelity has host-specific effects on replication in cell culture and is associated with nearly complete ablation of WNV infection in mosquito vectors. These results have significant implications for our understanding of arbovirus evolution, replication complex function and arboviral fitness in mosquitoes, and identify important targets to study the determinants and mechanisms of vector competence and arbovirus fidelity.


Vyšlo v časopise: Sequence-Specific Fidelity Alterations Associated with West Nile Virus Attenuation in Mosquitoes. PLoS Pathog 11(6): e32767. doi:10.1371/journal.ppat.1005009
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1005009

Souhrn

West Nile virus (WNV) is the most geographically widespread arthropod-borne virus (arbovirus) in the world. Like most arboviruses, WNV is a RNA virus which is highly mutable and exists in nature as genetically diverse mutant swarms. Although many recent studies have investigated the relationship between virus mutation rate and viral fitness, this had not previously been determined for WNV or other flaviviruses. We identified WNV mutations associated with variation in mutation rate using cell culture passage in the presence of a mutagen and engineered these mutations into an infectious WNV clone in order to investigate the causes and consequences of altered fidelity. Our results demonstrate that interactions among proteins which comprise the WNV replication complex can significantly alter both the extent and types of mutations that occur. In addition, we show that both increasing and decreasing WNV fidelity has host-specific effects on replication in cell culture and is associated with nearly complete ablation of WNV infection in mosquito vectors. These results have significant implications for our understanding of arbovirus evolution, replication complex function and arboviral fitness in mosquitoes, and identify important targets to study the determinants and mechanisms of vector competence and arbovirus fidelity.


Zdroje

1. Sanjuan R, Nebot MR, Chirico N, Mansky LM, Belshaw R. Viral mutation rates. J Virol. 2010; 84: 9733–9748. doi: 10.1128/JVI.00694-10 20660197

2. Duffy S, Shackelton LA, Holmes EC. Rates of evolutionary change in viruses: patterns and determinants. Nat Rev Genet. 2008; 9: 267–276. doi: 10.1038/nrg2323 18319742

3. Drake JW, Holland JJ. Mutation rates among RNA viruses. Proc Natl Acad Sci U S A. 1999; 96: 13910–13913. 10570172

4. Holland JJ, Spindler K, Horodyski F, Grabau E, Nichol S, VandePol S. Rapid evolution of RNA genomes. Science. 1982; 215: 1577–1585. 7041255

5. Duarte EA, Novella IS, Weaver SC, Domingo E, Wain-Hobson S, Clarke DK, Moya A, Elena SF, de la Torre JC, Holland JJ. RNA virus quasispecies: significance for viral disease and epidemiology. Infect Agents Dis. 1994; 3: 201–214. 7827789

6. Vignuzzi M, Stone JK, Arnold JJ, Cameron CE, Andino R. Quasispecies diversity determines pathogenesis through cooperative interactions in a viral population. Nature. 2006; 439: 344–348. 16327776

7. Furio V, Moya A, Sanjuan R. The cost of replication fidelity in an RNA virus. Proc Natl Acad Sci U S A. 2005; 102: 10233–10237. 16006529

8. Furio V, Moya A, Sanjuan R. The cost of replication fidelity in human immunodeficiency virus type 1. Proc Biol Sci. 2007; 274: 225–230. 17148251

9. Arnold JJ, Vignuzzi M, Stone JK, Andino R, Cameron CE. Remote Site Control of an Active Site Fidelity Checkpoint in a Viral RNA-dependent RNA Polymerase. J Biol Chem. 2005; 280: 25706–25716. 15878882

10. Pfeiffer JK, Kirkegaard K. Increased Fidelity Reduces Poliovirus Fitness and Virulence under Selective Pressure in Mice. PLoS Pathog. 2005; 1: e11. 16220146

11. Vignuzzi M, Stone JK, Andino R. Ribavirin and lethal mutagenesis of poliovirus: molecular mechanisms, resistance and biological implications. Virus Res. 2005; 107: 173–181. 15649563

12. Bull JJ, Sanjuan R, Wilke CO. Theory of lethal mutagenesis for viruses. J Virol. 2007; 81: 2930–2939. 17202214

13. Domingo E. Viruses at the edge of adaptation. Virology. 2000; 270: 251–253. 10792982

14. Crance JM, Scaramozzino N, Jouan A, Garin D. Interferon, ribavirin, 6-azauridine and glycyrrhizin: antiviral compounds active against pathogenic flaviviruses Antiviral Res. 2003; 58: 73–79. 12719009

15. Crotty S, Maag D, Arnold JJ, Zhong W, Lau JYN, Hong Z, Andino R, Cameron CE. The broad-spectrum antiviral ribonucleoside ribavirin is an RNA virus mutagen. Nat Med. 2000; 6: 1375–1379. 11100123

16. Graham RL, Becker MM, Eckerle LD, Bolles M, Denison MR, Baric RS. A live, impaired-fidelity coronavirus vaccine protects in an aged, immunocompromised mouse model of lethal disease. Nat Med. 2012; 18: 1820–1826. doi: 10.1038/nm.2972 23142821

17. Korboukh VK, Lee CA, Acevedo A, Vignuzzi M, Xiao Y, Arnold JJ, Hemperly S, Graci JD, August A, Andino R, Cameron CE. RNA virus population diversity, an optimum for maximal fitness and virulence. J Biol Chem. 2014; 289: 29531–29544. doi: 10.1074/jbc.M114.592303 25213864

18. Gnadig NF, Beaucourt S, Campagnola G, Borderia AV, Sanz-Ramos M, Gong P, Blanc H, Peersen OB, Vignuzzi M. Coxsackievirus B3 mutator strains are attenuated in vivo. Proc Natl Acad Sci U S A. 2012; 109: E2294–E2303. doi: 10.1073/pnas.1204022109 22853955

19. Rozen-Gagnon K, Stapleford KA, Mongelli V, Blanc H, Failloux AB, Saleh MC, Vignuzzi M. Alphavirus mutator variants present host-specific defects and attenuation in mammalian and insect models. PLoS Pathog. 2014; 10: e1003877. doi: 10.1371/journal.ppat.1003877 24453971

20. Weeks SA, Lee CA, Zhao Y, Smidansky ED, August A, Arnold JJ, Cameron CE. A Polymerase mechanism-based strategy for viral attenuation and vaccine development. J Biol Chem. 2012; 287: 31618–31622. doi: 10.1074/jbc.C112.401471 22854962

21. Levi LI, Gnadig NF, Beaucourt S, McPherson MJ, Baron B, Arnold JJ, Vignuzzi M. Fidelity variants of RNA dependent RNA polymerases uncover an indirect, mutagenic activity of amiloride compounds. PLoS Pathog. 2010; 6: e1001163. doi: 10.1371/journal.ppat.1001163 21060812

22. Zeng J, Wang H, Xie X, Li C, Zhou G, Yang D, Yu L. Ribavirin-resistant variants of foot-and-mouth disease virus: the effect of restricted quasispecies diversity on viral virulence. J Virol. 2014; 88: 4008–4020. doi: 10.1128/JVI.03594-13 24453363

23. Zeng J, Wang H, Xie X, Yang D, Zhou G, Yu L. An increased replication fidelity mutant of foot-and-mouth disease virus retains fitness in vitro and virulence in vivo. Antiviral Res. 2013; 100: 1–7. doi: 10.1016/j.antiviral.2013.07.008 23880348

24. Coffey LL, Beeharry Y, Borderia AV, Blanc H, Vignuzzi M. Arbovirus high fidelity variant loses fitness in mosquitoes and mice. Proc Natl Acad Sci U S A. 2011; 108: 16038–16043. doi: 10.1073/pnas.1111650108 21896755

25. Pfeiffer JK, Kirkegaard K. 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. 2003; 100: 7289–7294. 12754380

26. Ciota AT, Kramer LD. Insights into Arbovirus Evolution and Adaptation from Experimental Studies. Viruses. 2010; 2: 2594–2617. doi: 10.3390/v2122594 21994633

27. Combe M, Sanjuan R. Variation in RNA virus mutation rates across host cells. PLoS Pathog. 2014; 10: e1003855. doi: 10.1371/journal.ppat.1003855 24465205

28. Ciota AT, Lovelace AO, Jia Y, Davis LJ, Young DS, Kramer LD. Characterization of mosquito-adapted West Nile virus. J Gen Virol. 2008; 89: 1633–1642. doi: 10.1099/vir.0.2008/000893-0 18559933

29. Jerzak G, Bernard KA, Kramer LD, Ebel GD. Genetic variation in West Nile virus from naturally infected mosquitoes and birds suggests quasispecies structure and strong purifying selection. J Gen Virol. 2005; 86: 2175–2183. 16033965

30. Fitzpatrick KA, Deardorff ER, Pesko K, Brackney DE, Zhang B, Bedrick E, Shi PY, Ebel GD. Population variation of West Nile virus confers a host-specific fitness benefit in mosquitoes. Virology. 2010; 404: 89–95. doi: 10.1016/j.virol.2010.04.029 20552731

31. Jerzak GV, Bernard K, Kramer LD, Shi PY, Ebel GD. The West Nile virus mutant spectrum is host-dependant and a determinant of mortality in mice. Virology. 2007; 360: 469–476. 17134731

32. Ciota AT, Ngo KA, Lovelace AO, Payne AF, Zhou Y, Shi P-Y, Kramer LD. Role of the mutant spectrum in adaptation and replication of West Nile virus. J Gen Virol. 2007; 88: 865–874. 17325359

33. Shi PY, Tilgner M, Lo MK, Kent KA, Bernard KA. Infectious cDNA clone of the epidemic West Nile virus from New York City. J Virol. 2002; 76: 5847–5856. 12021317

34. Payne AF, Binduga-Gajewska I, Kauffman EB, Kramer LD. Quantitation of flaviviruses by fluorescent focus assay. J Virol Methods. 2006; 134: 183–187. 16510196

35. Huang L, Sineva EV, Hargittai MR, Sharma SD, Suthar M, Raney KD, Cameron CE. Purification and characterization of hepatitis C virus non-structural protein 5A expressed in Escherichia coli. Protein Expr Purif. 2004; 37: 144–153. 15294292

36. Studier FW (2005) Protein production by auto-induction in high density shaking cultures. Protein Expr Purif 41: 207–234. 15915565

37. Shi P-Y, Kauffman EB, Ren P, Felton A., Tai JH, Dupuis AP II, Jones SA, Ngo KA, Nicholas DC, Maffei JG, Ebel GD, Bernard KA, Kramer LD. High throughput detection of West Nile virus RNA. J Clin Microbiol. 2001; 39: 1264–1271. 11283039

38. Ebel GD, Rochlin I, Longacker J, Kramer LD. Culex restuans (Diptera:culicidae) relative abundance and vector competence for West Nile virus. J Med Entomol. 2005; 42: 838–843. 16363169

39. Butcher SJ, Grimes JM, Makeyev E, V, Bamford DH, Stuart DL. A mechanism for initiating RNA-dependent RNA polymerization. Nature. 2001; 410: 235. 11242087

40. Bressanelli S, Tomei L, Rey FA, De FR. Structural analysis of the hepatitis C virus RNA polymerase in complex with ribonucleotides. J Virol. 2002; 76: 3482–3492. 11884572

41. Zhou Y, Ray D, Zhao Y, Dong H, Ren S, Li Z, Guo Y, Bernard KA, Shi P-Y, Li H. Structure and function of Flavivirus NS5 methyltransferase. J Virol. 2007; 81: 3891–3903. 17267492

42. Malet H, Egloff MP, Selisko B, Butcher RE, Wright PJ, Roberts M, Gruez A, Sulzenbacher G, Vonrhein C, Bricogne G, Mackenzie JM, Khromykh AA, Davidson AD, Canard B. Crystal structure of the RNA polymerase domain of the West Nile virus non-structural protein 5. J Biol Chem. 2002; 282: 10678–10689.

43. Komar N, Langevin S, Hinten S, Nemeth N, Edwards E, Hettler D, Davis B, Bowen R, Bunning M (2003) Experimental infection of North American birds with the New York 1999 strain of West Nile virus. Emerg Infect Dis 9: 311–322. 12643825

44. Sadeghipour S, McMinn PC (2013) A study of the virulence in mice of high copying fidelity variants of human enterovirus 71. Virus Res 176: 265–272. doi: 10.1016/j.virusres.2013.06.019 23856384

45. Day CW, Smee DF, Julander JG, Yamshchikov VF, Sidwell RW, Morrey JD. Error-prone replication of West Nile virus caused by ribavirin. Antiviral Res. 2005; 67: 38–45. 15919121

46. Denison MR, Graham RL, Donaldson EF, Eckerle LD, Baric RS. Coronaviruses: an RNA proofreading machine regulates replication fidelity and diversity. RNA Biol. 2011; 8: 270–279. 21593585

47. Zhao Y, Soh TS, Zheng J, Chan KW, Phoo WW, Lee CC, Tay MY, Swaminathan K, Cornvik TC, Lim SP, Shi PY, Lescar J, Vasudevan SG, Luo D. A Crystal Structure of the Dengue Virus NS5 Protein Reveals a Novel Inter-domain Interface Essential for Protein Flexibility and Virus Replication. PLoS Pathog. 2015; 11: e1004682. doi: 10.1371/journal.ppat.1004682 25775415

48. Butcher SJ, Grimes JM, Makeyev EV, Bamford DH, Stuart DI (2001) A mechanism for initiating RNA-dependent RNA polymerization. Nature. 2001 410: 235–240. 11242087

49. Moustafa IM, Korboukh VK, Arnold JJ, Smidansky ED, Marcotte LL, Gohara DW, Yang X, Sanchez-Farran MA, Filman D, Maranas JK, Boehr DD, Hogle JM, Colina CM, Cameron CE. Structural Dynamics as a Contributor to Error-prone Replication by a RNA-dependent RNA Polymerase. J Biol Chem. 2014; 26;289 (52):36229–48. doi: 10.1074/jbc.M114.616193 25378410

50. Moustafa IM, Shen H, Morton B, Colina CM, Cameron CE. Molecular dynamics simulations of viral RNA polymerases link conserved and correlated motions of functional elements to fidelity. J Mol Biol. 2011; 410: 159–181. doi: 10.1016/j.jmb.2011.04.078 21575642

51. Zhang B, Dong H, Zhou Y, Shi PY. Genetic interactions among the West Nile virus methyltransferase, the RNA-dependent RNA polymerase, and the 5' stem-loop of genomic RNA. J Virol. 2008 82: 7047–7058. doi: 10.1128/JVI.00654-08 18448528

52. Lu G, Gong P. Crystal Structure of the full-length Japanese encephalitis virus NS5 reveals a conserved methyltransferase-polymerase interface. PLoS Pathog. 2013; 9: e1003549. doi: 10.1371/journal.ppat.1003549 23950717

53. Cameron CE, Moustafa IM, Arnold JJ. Dynamics: the missing link between structure and function of the viral RNA-dependent RNA polymerase? Curr Opin Struct Biol. 2009; 19: 768–774. doi: 10.1016/j.sbi.2009.10.012 19910183

54. Yang X, Welch JL, Arnold JJ, Boehr DD. Long-range interaction networks in the function and fidelity of poliovirus RNA-dependent RNA polymerase studied by nuclear magnetic resonance. Biochemistry. 2010; 49: 9361–9371. doi: 10.1021/bi100833r 20860410

55. Arias A, Arnold JJ, Sierra M, Smidansky ED, Domingo E, Cameron CE. 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 2008; 82: 12346–12355. doi: 10.1128/JVI.01297-08 18829745

56. Leyssen P, De Clercq E, Neyts J. The Anti-Yellow Fever Virus Activity of Ribavirin Is Independent of Error-Prone Replication. Mol Pharmacol. 2006; 69: 1461–1467. 16421290

57. Cassidy LF, Patterson JL. Mechanism of La Crosse virus inhibition by ribavirin. Antimicrob Agents Chemother. 1989; 33: 2009–2011. 2610511

58. Benarroch D, Egloff MP, Mulard L, Guerreiro C, Romette JL, Canard B. A structural basis for the inhibition of the NS5 dengue virus mRNA 2'-O-methyltransferase domain by ribavirin 5'-triphosphate. J Biol Chem. 2004; 279: 35638–35643. 15152003

59. Goswami BB, Borek E, Sharma OK, Fujitaki J, Smith RA. The broad spectrum antiviral agent ribavirin inhibits capping of mRNA. Biochem Biophys Res Commun. 1979; 89: 830–836. 226095

60. Chambers TJ, Hahn CS, Galler R, Rice CM. Flavivirus genome organization, expression, and replication. Annu Rev Microbiol. 1990; 44: 649–688. 2174669

61. Egloff MP, Benarroch D, Selisko B, Romette JL, Canard B. An RNA cap (nucleoside-2'-O-)-methyltransferase in the flavivirus RNA polymerase NS5: crystal structure and functional characterization. EMBO J. 2002; 21: 2757–2768. 12032088

62. Ciota AT, Jia Y, Payne AF, Jerzak G, Davis LJ, Young DS, Ehrbar D, Kramer LD. Experimental passage of St. Louis encephalitis virus in vivo in mosquitoes and chickens reveals evolutionarily significant virus characteristics. PLoS One. 2009; 4: e7876. doi: 10.1371/journal.pone.0007876 19924238

63. Brackney DE, Beane JE, Ebel GD. RNAi targeting of West Nile virus in mosquito midguts promotes virus diversification. PLoS Pathog. 2009; 5: e1000502. doi: 10.1371/journal.ppat.1000502 19578437

64. Ciota AT, Ehrbar DJ, Van Slyke GA, Willsey GG, Kramer LD. Cooperative interactions in the West Nile virus mutant swarm. BMC Evol Biol. 2012; 12: 58. doi: 10.1186/1471-2148-12-58 22541042

65. Jerzak GV, Brown I, Shi PY, Kramer LD, Ebel GD. Genetic diversity and purifying selection in West Nile virus populations are maintained during host switching. Virology. 2008; 374: 256–260. doi: 10.1016/j.virol.2008.02.032 18395240

66. Ciota AT, Payne AF, Ngo K, Kramer L (2014) Consequences of in vitro host shift for St. Louis encephalitis virus. J Gen Virol. vir.0.063545–0 [pii];doi: 10.1099/vir.0.063545-0

67. Ebel GD, Fitzpatrick KA, Lim PY, Bennett CJ, Deardorff ER, Jerzak GV, Kramer LD, Zhou Y, Shi PY, Bernard KA. Nonconsensus West Nile virus genomes arising during mosquito infection suppress pathogenesis and modulate virus fitness in vivo. J Virol. 2011; 85: 12605–12613. doi: 10.1128/JVI.05637-11 21937657

68. Pita JS, de Miranda JR, Schneider WL, Roossinck MJ. Environment determines fidelity for an RNA virus replicase. J Virol. 2007; 81: 9072–9077. 17553888

69. Acevedo A, Brodsky L, Andino R. Mutational and fitness landscapes of an RNA virus revealed through population sequencing. Nature. 2014; 505: 686–690. doi: 10.1038/nature12861 24284629

70. Lou DI, Hussmann JA, McBee RM, Acevedo A, Andino R, Press WH, Sawyer SL. High-throughput DNA sequencing errors are reduced by orders of magnitude using circle sequencing. Proc Natl Acad Sci U S A. 2013; 110: 19872–19877. doi: 10.1073/pnas.1319590110 24243955

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Hygiena a epidemiológia Infekčné lekárstvo Laboratórium

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