Volume 89, Issue 2
  • ISSN: 0002-9637
  • E-ISSN: 1476-1645



In 2012, Texas experienced the largest outbreak of human West Nile encephalitis (WNE) since the introduction of West Nile virus (WNV) in 2002. Despite the large number of WNV infections, data indicated the rate of reported WNE among human cases was no higher than in previous years. To determine whether the increase in WNV human cases could have been caused by viral genetic changes, the complete genomes of 17 isolates made from mosquito pools in Dallas and Montgomery Counties in 2012 were sequenced. The 2012 Texas isolates were found to be composed of two distinct clades, both circulating in Dallas and Montgomery Counties despite a 5-fold higher disease incidence in the former. Although minor genetic differences existed between Dallas and Montgomery WNV populations, there was weak support for population subdivision or adaptive changes. On the basis of these data, alternative explanations for increased WNV disease incidence in 2012 are proposed.

[open-access] This is an Open Access article distributed under the terms of the American Society of Tropical Medicine and Hygiene's Re-use License which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.


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  1. CDC, 1999. Outbreak of West Nile-like viral encephalitis–New York, 1999. MMWR Morb Mortal Wkly Rep 48: 845849. [Google Scholar]
  2. CDC, 2002. Provisional surveillance summary of the West Nile virus epidemic–United States, January–November 2002. MMWR Morb Mortal Wkly Rep 51: 11291133. [Google Scholar]
  3. CDC, 2010. West Nile virus activity–United States, 2009. MMWR Morb Mortal Wkly Rep 59: 769772. [Google Scholar]
  4. CDC, 2011. West Nile virus disease and other arboviral diseases–United States, 2010. MMWR Morb Mortal Wkly Rep 60: 10091013. [Google Scholar]
  5. CDC, 2012. West Nile virus disease and other arboviral diseases–United States, 2011. MMWR Morb Mortal Wkly Rep 61: 510514. [Google Scholar]
  6. Lindsey NP, Staples JE, Lehman JA, Fischer M, Centers for Disease Control and Prevention (CDC); , 2010. Surveillance for human West Nile virus disease–United States, 1999–2008. MMWR Surveill Summ 59: 117. [Google Scholar]
  7. Petersen LR, Carson PJ, Biggerstaff BJ, Custer B, Borchardt SM, Busch MP, , 2012. Estimated cumulative incidence of West Nile virus infection in US adults, 1999–2010. Epidemiol Infect 28: 15. [Google Scholar]
  8. Petersen L, , 2012. Record heat may have contributed to a banner year for West Nile virus. Interview with Lyle Petersen. JAMA 308: 18461848.[Crossref] [Google Scholar]
  9. Jerzak G, Bernard KA, Kramer LD, Ebel GD, , 2005. Genetic variation in West Nile virus from naturally infected mosquitoes and birds suggests quasispecies structure and strong purifying selection. J Gen Virol 86: 21752183.[Crossref] [Google Scholar]
  10. Bertolotti L, Kitron U, Goldberg TL, , 2007. Diversity and evolution of West Nile virus in Illinois and the United States, 2002–2005. Virology 360: 143149.[Crossref] [Google Scholar]
  11. Pybus OG, Suchard MA, Lemey P, Bernardin FJ, Rambaut A, Crawford FW, Gray RR, Arinaminpathy N, Stramer SL, Busch MP, Delwart EL, , 2012. Unifying the spatial epidemiology and molecular evolution of emerging epidemics. Proc Natl Acad Sci USA 109: 1506615071.[Crossref] [Google Scholar]
  12. Gray RR, Veras NM, Santos LA, Salemi M, , 2010. Evolutionary characterization of the West Nile Virus complete genome. Mol Phylogenet Evol 56: 195200.[Crossref] [Google Scholar]
  13. Kilpatrick AM, Meola MA, Moudy RM, Kramer LD, , 2008. Temperature, viral genetics, and the transmission of West Nile virus by Culex pipiens mosquitoes. PLoS Pathog 4: e1000092.[Crossref] [Google Scholar]
  14. Moudy RM, Meola MA, Morin LL, Ebel GD, Kramer LD, , 2007. A newly emergent genotype of West Nile virus is transmitted earlier and more efficiently by Culex mosquitoes. Am J Trop Med Hyg 77: 365370. [Google Scholar]
  15. Davis CT, Ebel GD, Lanciotti RS, Brault AC, Guzman H, Siirin M, Lambert A, Parsons RE, Beasley DW, Novak RJ, Elizondo-Quiroga D, Green EN, Young DS, Stark LM, Drebot MA, Artsob H, Tesh RB, Kramer LD, Barrett AD, , 2005. Phylogenetic analysis of North American West Nile virus isolates, 2001–2004: evidence for the emergence of a dominant genotype. Virology 342: 252265.[Crossref] [Google Scholar]
  16. Ebel GD, Carricaburu J, Young D, Bernard KA, Kramer LD, , 2004. Genetic and phenotypic variation of West Nile virus in New York, 2000–2003. Am J Trop Med Hyg 71: 493500. [Google Scholar]
  17. Brault AC, Huang CY, Langevin SA, Kinney RM, Bowen RA, Ramey WN, Panella NA, Holmes EC, Powers AM, Miller BR, , 2007. A single positively selected West Nile viral mutation confers increased virogenesis in American crows. Nat Genet 39: 11621166.[Crossref] [Google Scholar]
  18. Sievers F, Wilm A, Dineen D, Gibson TJ, Karplus K, Li W, Lopez R, McWilliam H, Remmert M, Soding J, Thompson JD, Higgins DG, , 2011. Fast, scalable generation of high-quality protein multiple sequence alignments using Clustal Omega. Mol Syst Biol 7: 539.[Crossref] [Google Scholar]
  19. Kosakovsky Pond SL, Posada D, Gravenor MB, Woelk CH, Frost SD, , 2006. Automated phylogenetic detection of recombination using a genetic algorithm. Mol Biol Evol 23: 18911901.[Crossref] [Google Scholar]
  20. Darriba D, Taboada GL, Doallo R, Posada D, , 2012. jModelTest 2: more models, new heuristics and parallel computing. Nat Methods 9: 772.[Crossref] [Google Scholar]
  21. Guindon S, Gascuel O, , 2003. A simple, fast, and accurate algorithm to estimate large phylogenies by maximum likelihood. Syst Biol 52: 696704.[Crossref] [Google Scholar]
  22. Guindon S, Dufayard JF, Lefort V, Anisimova M, Hordijk W, Gascuel O, , 2010. New algorithms and methods to estimate maximum-likelihood phylogenies: assessing the performance of PhyML 3.0. Syst Biol 59: 307321.[Crossref] [Google Scholar]
  23. Tamura K, Nei M, Kumar S, , 2004. Prospects for inferring very large phylogenies by using the neighbor-joining method. Proc Natl Acad Sci USA 101: 1103011035.[Crossref] [Google Scholar]
  24. Tamura K, Peterson D, Peterson N, Stecher G, Nei M, Kumar S, , 2011. MEGA5: molecular evolutionary genetics analysis using maximum likelihood, evolutionary distance, and maximum parsimony methods. Mol Biol Evol 28: 27312739.[Crossref] [Google Scholar]
  25. Pond SL, Frost SD, , 2005. Datamonkey: rapid detection of selective pressure on individual sites of codon alignments. Bioinformatics 21: 25312533.[Crossref] [Google Scholar]
  26. Murrell B, Moola S, Mabona A, Weighill T, Sheward D, Kosakovsky Pond SL, Scheffler K, , 2013. FUBAR: A Fast, Unconstrained Bayesian AppRoximation for inferring selection. Mol Biol Evol 30: 11961205.[Crossref] [Google Scholar]
  27. Nolan MS, Schuermann J, Murray KO, , 2013. West Nile virus infection among humans, Texas, USA, 2002–2011. Emerg Infect Dis 19: 137139.[Crossref] [Google Scholar]
  28. Duggal NK, Emerman M, , 2012. Evolutionary conflicts between viruses and restriction factors shape immunity. Nat Rev Immunol 12: 687695.[Crossref] [Google Scholar]
  29. McMullen AR, May FJ, Li L, Guzman H, Bueno R, Jr Dennett JA, Tesh RB, Barrett AD, , 2011. Evolution of new genotype of West Nile virus in North America. Emerg Infect Dis 17: 785793.[Crossref] [Google Scholar]
  30. Brault AC, Langevin SA, Bowen RA, Panella NA, Biggerstaff BJ, Miller BR, Komar N, , 2004. Differential virulence of West Nile strains for American crows. Emerg Infect Dis 10: 21612168.[Crossref] [Google Scholar]
  31. Brackney DE, Beane JE, Ebel GD, , 2009. RNAi targeting of West Nile virus in mosquito midguts promotes virus diversification. PLoS Pathog 5: e1000502.[Crossref] [Google Scholar]
  32. Brackney DE, Pesko KN, Brown IK, Deardorff ER, Kawatachi J, Ebel GD, , 2011. West Nile virus genetic diversity is maintained during transmission by Culex pipiens quinquefasciatus mosquitoes. PLoS ONE 6: e24466.[Crossref] [Google Scholar]
  33. Amore G, Bertolotti L, Hamer GL, Kitron UD, Walker ED, Ruiz MO, Brawn JD, Goldberg TL, , 2010. Multi-year evolutionary dynamics of West Nile virus in suburban Chicago, USA, 2005–2007. Philos Trans R Soc Lond B Biol Sci 365: 18711878.[Crossref] [Google Scholar]
  34. Armstrong PM, Vossbrinck CR, Andreadis TG, Anderson JF, Pesko KN, Newman RM, Lennon NJ, Birren BW, Ebel GD, Henn MR, , 2011. Molecular evolution of West Nile virus in a northern temperate region: Connecticut, USA 1999–2008. Virology 417: 203210.[Crossref] [Google Scholar]
  35. Mann BR, McMullen AR, Guzman H, Tesh RB, Barrett AD, , 2013. Dynamic transmission of West Nile virus across the United States-Mexican border. Virology 436: 7580.[Crossref] [Google Scholar]
  36. Reisen WK, Fang Y, Martinez VM, , 2006. Effects of temperature on the transmission of West Nile virus by Culex tarsalis (Diptera: Culicidae). J Med Entomol 43: 309317.[Crossref] [Google Scholar]
  37. Hartley DM, Barker CM, Le Menach A, Niu T, Gaff HD, Reisen WK, , 2012. Effects of temperature on emergence and seasonality of West Nile virus in California. Am J Trop Med Hyg 86: 884894.[Crossref] [Google Scholar]
  38. Lanciotti RS, Roehrig JT, Deubel V, Smith J, Parker M, Steele K, Crise B, Volpe KE, Crabtree MB, Scherret JH, Hall RA, MacKenzie JS, Cropp CB, Panigrahy B, Ostlund E, Schmitt B, Malkinson M, Banet C, Weissman J, Komar N, Savage HM, Stone W, McNamara T, Gubler DJ, , 1999. Origin of the West Nile virus responsible for an outbreak of encephalitis in the northeastern United States. Science 286: 23332337.[Crossref] [Google Scholar]
  39. Anderson JF, Andreadis TG, Vossbrinck CR, Tirrell S, Wakem EM, French RA, Garmendia AE, Van Kruiningen HJ, , 1999. Isolation of West Nile virus from mosquitoes, crows, and a Cooper's hawk in Connecticut. Science 286: 23312333.[Crossref] [Google Scholar]
  40. Lanciotti RS, Ebel GD, Deubel V, Kerst AJ, Murri S, Meyer R, Bowen M, McKinney N, Morrill WE, Crabtree MB, Kramer LD, Roehrig JT, , 2002. Complete genome sequences and phylogenetic analysis of West Nile virus strains isolated from the United States, Europe, and the Middle East. Virology 298: 96105.[Crossref] [Google Scholar]
  41. Deardorff E, Estrada-Franco J, Brault AC, Navarro-Lopez R, Campomanes-Cortes A, Paz-Ramirez P, Solis-Hernandez M, Ramey WN, Davis CT, Beasley DW, Tesh RB, Barrett AD, Weaver SC, , 2006. Introductions of West Nile virus strains to Mexico. Emerg Infect Dis 12: 314318.[Crossref] [Google Scholar]
  42. Herring BL, Bernardin F, Caglioti S, Stramer S, Tobler L, Andrews W, Cheng L, Rampersad S, Cameron C, Saldanha J, Busch MP, Delwart E, , 2007. Phylogenetic analysis of WNV in North American blood donors during the 2003–2004 epidemic seasons. Virology 363: 220228.[Crossref] [Google Scholar]
  43. May FJ, Li L, Davis CT, Galbraith SE, Barrett AD, , 2010. Multiple pathways to the attenuation of West Nile virus in south-east Texas in 2003. Virology 405: 814.[Crossref] [Google Scholar]
  44. Andrade CC, Maharaj PD, Reisen WK, Brault AC, , 2011. North American West Nile virus genotype isolates demonstrate differential replicative capacities in response to temperature. J Gen Virol 92: 25232533.[Crossref] [Google Scholar]

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  • Received : 18 Mar 2013
  • Accepted : 14 May 2013
  • Published online : 07 Aug 2013

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