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Volume 14, Number 2—February 2008
Research

Genetic Determinants of Virulence in Pathogenic Lineage 2 West Nile Virus Strains

Elizabeth M. Botha*, Wanda Markotter*, Mariaan Wolfaardt*, Janusz T. Paweska†, Robert Swanepoel†, Gustavio Palacios‡, Louis H. Nel*, and Marietjie Venter*Comments to Author 
Author affiliations: *University of Pretoria, Pretoria, South Africa; †National Institute for Communicable Diseases, Sandringham, South Africa; ‡Columbia University, New York, New York, USA;

Main Article

Table 4

Summary of cleavage scores predicted for cleavage junctions of proteins of West Nile virus strains*

SA381/ 00 H442 SPU116/ 89 SA93/01 B956D117B3 AnMg798 NY-385–99 NY-385–99 clone TYP-9376 NY-385–99 clone 9317B TM171–03 MRM61C p value†
Between capsid and premembrane proteins
G +3.69 +3.69 +3.69 +3.69 +3.69 +4.00 −0.49 −0.49 −0.49 −0.49 −1.85 0.00005
A‡ +9.37 +9.37 +9.37 +9.37 +9.37 +8.01 +5.93 +5.93 +5.93 +5.93 +7.37 0.00004
V
 −9.14
 −9.14
 −9.14
 −9.14
 −9.14
 −7.8
 −9.52
 −9.52
 −9.52
 −9.52
 −10.32
 0.02235
Between premembrane and envelope proteins
Y −10.15 −10.15 −10.15 −10.15 −10.15 −9.12 −9.12 −9.12 −9.12 −9.12 −9.45 0.00433
S‡ +11.27 +11.27 +11.27 +11.27 +11.27 +12.42 +12.42 +12.42 +12.42 +12.42 +11.50 0.01728
F
 −5.37
 −5.37
 −5.37
 −5.37
 −5.37
 −4.78
 −4.78
 −4.78
 −4.78
 −4.78
 −5.27
 0.01977
Between envelope protein and nonstructural protein 1
H −9.01 −9.01 −9.01 −9.01 −9.01 −9.71 −9.01 −9.01 −9.01 −9.01 −9.01 0.36322
A‡ +4.26 +4.26 +4.26 +4.26 +4.26 +4.04 +4.26 +4.26 +4.26 +4.26 +4.26 0.36322
D
 −11.05
 −11.05
 −11.05
 −11.05
 −11.05
 −11.15
 −11.05
 −11.05
 −11.05
 −11.05
 −11.05
 0.36322
Between nonstructural proteins 4B and 5
R −16.05 −16.05 −16.05 −16.05 −16.05 −16.05 −16.05 −16.05 −16.05 −15.83 −16.05 0.37390
G‡ −13.19 −13.19 −13.19 −13.19 −13.19 −13.19 −13.19 −13.19 −13.19 −13.08 −13.19 0.37390
G −19.54 −19.54 −19.54 −19.54 −19.54 −19.54 −19.54 −19.54 −19.54 −19.66 −19.54 0.37390

*Signal cleavage predicted scores were calculated with AnalyzeSignalase 2.03 (14). The table indicates only the last amino acid of the first protein and the first 2 amino acids of the following protein.
†Two-tailed Student t test results, indicating the probability of significance of observed differences between lineage 2 and lineage 1 strains.
‡Exact cleavage site.

Main Article

References
  1. Petersen  LR, Roehrig  JT. West Nile virus: a reemerging global pathogen. Emerg Infect Dis. 2001;7:611–4.PubMedGoogle Scholar
  2. Beasley  DW, Li  L, Suderman  MT, Barrett  AD. Mouse neuroinvasive phenotype of West Nile virus strains varies depending upon virus genotype. Virology. 2002;296:17–23. DOIPubMedGoogle Scholar
  3. Burt  FJ, Grobbelaar  AA, Leman  PA, Anthony  FS, Gibson  GV, Swanepoel  R. Phylogenetic relationships of southern African West Nile virus isolates. Emerg Infect Dis. 2002;8:820–6.PubMedGoogle Scholar
  4. Venter  M, Myers  TG, Wilson  MA, Kindt  TJ, Paweska  JT, Burt  FJ, Gene expression in mice infected with West Nile virus strains of different neurovirulence. Virology. 2005;342:119–40. DOIPubMedGoogle Scholar
  5. Bakonyi  T, Ivanics  E, Erdelyi  K, Ursu  K, Ferenczi  E, Weissenbock  H, Lineage 1 and 2 strains of encephalitic West Nile virus, central Europe. Emerg Infect Dis. 2006;12:618–23.PubMedGoogle Scholar
  6. Beasley  DW, Whiteman  MC, Zhang  S, Huang  CY, Schneider  BS, Smith  DR, Envelope protein glycosylation status influences mouse neuroinvasion phenotype of genetic lineage 1 West Nile virus strains. J Virol. 2005;79:8339–47. DOIPubMedGoogle Scholar
  7. Yamshchikov  G, Borisevich  V, Seregin  A, Chaporgina  E, Mishina  M, Mishin  V, An attenuated West Nile prototype virus is highly immunogenic and protects against the deadly NY99 strain: a candidate for live WNV vaccine development. Virology. 2004;330:304–12. DOIPubMedGoogle Scholar
  8. Wicker  JA, Whiteman  MC, Beasley  DWC, Davis  CT, Zhang  S, Schneider  BS, A single amino acid substitution in the central portion of the West Nile virus NS4B protein confers a highly attenuated phenotype in mice. Virology. 2006;349:245–53. DOIPubMedGoogle Scholar
  9. Puig-Basagoiti  F, Tilgner  M, Bennett  CJ, Yangsheng  Z, Munoz-Jordan  JL, Garcia-Sastre  A, A mouse cell-adapted NS4B mutation attenuates West Nile virus RNA synthesis. Virology. 2007;361:229–41. DOIPubMedGoogle Scholar
  10. Kinney  RM, Huang  CY-H, Whiteman  MC, Bowen  RA, Langevin  SA, Miller  BR, Avian virulence and thermostable replication of the North American strain of West Nile virus. J Gen Virol. 2006;87:3611–22. DOIPubMedGoogle Scholar
  11. Thompson  JD, Higgins  DG, Gibson  TJ. CLUSTAL W: improving the sensitivity of progressive multiple sequence alignment through sequence weighting, position-specific gap penalties and weight matrix choice. Nucleic Acids Res. 1994;22:4673–80. DOIPubMedGoogle Scholar
  12. Nicholas  KB, Nicholas  HB Jr. GeneDoc: a tool for editing and annotating multiple sequence alignments; 1997 [available from author].
  13. Kumar  S, Tamura  K, Nei  M. MEGA3: integrated software for molecular evolutionary genetics analysis and sequence alignment. Brief Bioinform. 2004;5:150–63. DOIPubMedGoogle Scholar
  14. Von Heijne  G. A new method for predicting signal sequence cleavage sites. Nucleic Acids Res. 1986;14:4683–90. DOIPubMedGoogle Scholar
  15. Castle  E, Nowak  T, Leidner  U, Wengler  G, Wengler  G. Sequence analysis of the viral core protein and the membrane-associated proteins V1 and NV2 of the flavivirus West Nile virus and the genome sequence of these proteins. Virology. 1985;145:227–36. DOIPubMedGoogle Scholar
  16. Keller  BC, Fredericksen  BL, Samuel  MA, Mock  RE, Mason  PW, Diamond  MS, Resistance to alpha/beta interferon is a determinant of West Nile virus replication fitness and virulence. J Virol. 2006;80:9424–34. DOIPubMedGoogle Scholar
  17. Borisevich  V, Seregin  A, Nistler  R, Mutabazi  D, Yamshchikov  V. Biological properties of chimeric West Nile viruses. Virology. 2006;349:371–81. DOIPubMedGoogle Scholar
  18. Ding  X, Wu  X, Duan  T, Siirin  M, Guzman  H, Yang  Z, Nucleotide and amino acid changes in West Nile virus strains exhibiting renal tropism in hamsters. Am J Trop Med Hyg. 2005;73:803–7.PubMedGoogle Scholar
  19. Beasley  DW, Davis  CT, Estrada-Franco  J, Navarro-Lopez  R, Campomanes-Cortes  A, Tesh  RB, Genome sequence and attenuating mutations in West Nile virus isolate from Mexico. Emerg Infect Dis. 2004;10:2221–4.PubMedGoogle Scholar
  20. Coia  G, Parker  MD, Speight  G, Byrne  ME, Westaway  EG. Nucleotide and complete amino acid sequences of Kunjin virus: definitive gene order and characteristics of the virus-specified protein. J Gen Virol. 1988;69:1–21. DOIPubMedGoogle Scholar
  21. Lanciotti  RS, Roehrig  JT, Deubel  V, Smith  J, Parker  M, Steele  K, Origin of the West Nile virus responsible for an outbreak of encephalitis in the northeastern United States. Science. 1999;286:2333–7. DOIPubMedGoogle Scholar
  22. Smithburn  KC, Hughes  TP, Burke  AV, Paul  JH. A neurotropic virus isolated from the blood of a native Ugandan. Am J Trop Med Hyg. 1940;20:471–92.
  23. Bondre  VP, Jadi  RS, Mishra  AC, Yergolkar  PN, Arankalle  VA. West Nile virus isolates from India: evidence for a distinct genetic lineage. J Gen Virol. 2007;88:875–84. DOIPubMedGoogle Scholar
  24. Campbell  GL, Marfin  AA, Lanciotti  RS, Gubler  DJ. West Nile virus. Lancet Infect Dis. 2002;2:519–29. DOIPubMedGoogle Scholar
  25. Lindenbach  BD, Rice  CM. Molecular biology of flaviviruses. Adv Virus Res. 2003;59:23–61. DOIPubMedGoogle Scholar
  26. Li  W, Brinton  MA. The 3′ stem loop of the West Nile virus genomic RNA can suppress translation of chimeric mRNAs. Virology. 2001;287:49–61. DOIPubMedGoogle Scholar
  27. Shurtleff  AC, Beasley  DW, Chen  JJ, Ni  H, Suderman  MT, Wang  H, Genetic variation in the 3′ non-coding region of dengue viruses. Virology. 2001;281:75–87. DOIPubMedGoogle Scholar
  28. Hurrelbrink  RJ, McMinn  PC. Molecular determinants of virulence: the structural and functional basis for flavivirus attenuation. Adv Virus Res. 2003;60:1–42. DOIPubMedGoogle Scholar
  29. Beasley  DWC. Recent advances in the molecular biology of West Nile virus. Curr Mol Med. 2005;5:835–50. DOIPubMedGoogle Scholar
  30. Davis  CT, Beasley  DWC, Guzman  H, Siirin  M, Parsons  RE, Tesh  RB, Emergence of attenuated West Nile virus variants in Texas, 2003. Virology. 2004;330:342–50. DOIPubMedGoogle Scholar
  31. Lee  E, Stocks  CE, Amberg  SM, Rice  CM, Lobigs  M. Mutagenesis of the signal sequence of yellow fever virus prM protein: enhancement of signalase cleavage in vitro is lethal for virus production. J Virol. 2000;74:24–32.PubMedGoogle Scholar
  32. Stocks  CE, Lobigs  M. Signal peptidase cleavage at the flavivirus C-prM junction: dependence on the viral NS2B–3 protease for efficient processing requires determinants in C, the signal peptide, and prM. J Virol. 1998;72:2141–9.PubMedGoogle Scholar

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Page created: July 07, 2010
Page updated: July 07, 2010
Page reviewed: July 07, 2010
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