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The virology, epidemiology, and clinical impact of West Nile virus: a decade of advancements in research since its introduction into the Western Hemisphere

  • K. O. MURRAY (a1), C. WALKER (a1) and E. GOULD (a2) (a3)

West Nile virus (WNV) is now endemic in the USA. After the widespread surge of virus activity across the USA, research has flourished, and our knowledge base has significantly expanded over the past 10 years since WNV was first recognized in New York City. This article provides a review of the virology of WNV, history, epidemiology, clinical features, pathology of infection, the innate and adaptive immune response, host risk factors for developing severe disease, clinical sequelae following severe disease, chronic infection, and the future of prevention.

Corresponding author
*Author for correspondence: Dr K. O. Murray, Assistant Professor of Epidemiology, The University of Texas Health Science Center at Houston, Center for Infectious Diseases, School of Public Health, Houston, TX, USA. (Email:
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1.ICTVdB Management (2006). Flavivirus. In: ICTVdB – The Universal Virus Database, version 4. Büchen-Osmond C, ed. Columbia University, New York, USA.
2.Hayes CG. West Nile virus: Uganda, 1937, to New York City, 1999. Annals of the New York Academy of Science 2001; 951: 2537.
3.Petersen LR, Roehrig JT. West Nile Virus: a reemerging global pathogen. Emerging Infectious Diseases 2001; 7: 611614.
4.Granwehr BP, et al. West Nile virus: where are we now? Lancet Infectious Diseases 2004; 4: 547556.
5.Higgs S, Snow K, Gould E. The potential for West Nile virus to establish outside of its natural range: a consideration of potential mosquito vectors in the United Kingdom. Transcripts of the Royal Society of Tropical Medicine and Hygiene 2004; 98: 8287.
6.Heinz-Taheny KM, et al. West Nile virus infection in free-ranging squirrels in Illinois. Journal of Veterinary Diagnostic Investigation 2004; 16: 186–90.
7.1.Miller DL, et al. West Nile virus in farmed alligators. Emerging Infectious Diseases 2003; 9: 794–9.
8.Cernescu C, et al. High number of severe neurologic clinical forms during an epidemic of West Nile Virus infection. Romanian Journal of Virology 1997; 48: 1325.
9.Tsai TF, et al. West Nile encephalitis epidemic in southeastern Romania. Lancet 1998; 352: 767771.
10.Platonov AE, et al. Outbreak of West Nile virus infection, Volgograd region, Russia, 1999. Emerging Infectious Diseases 2001; 7: 128132.
11.Lanciotti RS, et al. Complete genomic sequences and phylogenetic analysis of West Nile strains isolated from the United States, Europe, and the Middle East. Virology 2002; 298: 96105.
12.CDC. Intrauterine West Nile virus infection – New York, 2002. Morbidity and Mortality Weekly Report 2002; 51: 11351136.
13.Biggerstaff BJ, Petersen LR. Estimated risk of West Nile virus transmission through transfusion during an epidemic in Queens, New York City. Transfusion 2002; 42: 10191026.
14.CDC. Update: investigations of West Nile virus infections in recipients of organ transplantation and blood transfusion. Morbidity and Mortality Weekly Report 2002; 51: 833836.
15.CDC. Investigations of West Nile virus infections in recipients of blood transfusions. Morbidity and Mortality Weekly Report 2002; 51: 973974.
16.Nash D, et al. The outbreak of West Nile virus infection in the New York City area in 1999. New England Journal of Medicine 2001; 344: 18071814.
17.CDC. Outbreak of West Nile-like viral encephalitis – New York, 1999. Morbidity and Mortality Weekly Report 1999; 48: 845849.
18.Jia XY, et al. Genetic analysis of West Nile New York 1999 encephalitis virus. Lancet 1999; 354: 19711972.
19.Lanciotti RS, et al. Origin of the West Nile virus responsible for an outbreak of encephalitis in the northeastern United States. Science 1999; 286: 23332337.
20.Campbell GL, et al. West Nile Virus. Lancet Infectious Disease 2002; 2: 519529.
21.Artsob H, et al. West Nile Virus in the New world – trends in the spread and proliferation of West Nile virus in the New World. Zoonoses and Public Health 2009; 56: 357369.
22.CDC. Provisional surveillance summary of the West Nile virus epidemic – United States, January–November 2002. Morbidity and Mortality Weekly Report 2002; 51: 11291133.
23.CDC.West Nile Virus ( Accessed 23 February 2010.
24.Pepperell C, et al. West Nile virus infection in 2002: morbidity and mortality among patients admitted to hospital in southcentral Ontario. Canadian Medical Association Journal 2003; 168: 13991405.
25.Komar N, Clark GG. West Nile virus activity in Latin America and the Caribbean. Revista Panamericana Salud Publica 2006; 19: 112117.
26.Mostashari F, et al. Epidemic West Nile encephalitis, New York, 1999: results of a household-based seroepidemiological survey. Lancet 2001; 358: 261264.
27.Brown JA, et al. West Nile viremic blood donors and risk factors for subsequent West Nile fever. Vector-Borne and Zoonotic Diseases 2007#x003B; 7: 479488.
28.Craven RB, Roehrig JT. West Nile Virus. Journal of the American Medical Association 2001; 344: 18581859.
29.Brilla R, et al. Clinical and neuroradiologic features of 39 consecutive cases of West Nile virus meningoencephalitis. Journal of Neurological Sciences 2004; 220: 3740.
30.Hayes EB, et al. Virology, pathology and clinical manifestations of West Nile virus disease. Emerging Infectious Diseases 2005; 11: 11741179
31.Watson JT, et al. Clinical characteristics and functional outcomes of West Nile Fever. Annals of Internal Medicine 2004; 141: 360365.
32.Asnis DS, et al. The West Nile virus encephalitis outbreak in the United States (1999–2000): from Flushing, New York, to beyond its borders. Annals of the New York Academy of Science 2001; 951: 161171.
33.Murray KO, et al. Clinical investigation of hospitalized human cases of West Nile virus infection in Houston, Texas, 2002–2004. Vector Borne and Zoonotic Diseases 2008; 8: 167–74.
34.Sejvar JJ, Haddad MB, Tierney BC. Neurologic manifestations and outcome of West Nile virus infection. Journal of the American Medical Association 2003; 290: 511515.
35.Ahmed S, et al. Guillain-Barré syndrome: an unusual presentation of West Nile Virus infection. Neurology 2000; 55: 144146.
36.CDC. Acute flaccid paralysis syndrome associated with West Nile virus infection – Mississippi and Louisiana, July–August 2002. Morbidity and Mortality Weekly Report 2002; 51: 826828.
37.Davis LE, et al. West Nile neuroinvasive disease. Annals of Neurology 2006; 60: 286300.
38.Saad M, et al. Acute flaccid paralysis: the spectrum of a newly recognized complication of West Nile virus infection. Journal of Infection 2005; 51: 120127.
39.Johnston LJ, Halliday GM, King NJ. Langerhans cells migrate to local lymph nodes following cutaneous infection with an arbovirus. Journal of Investigative Dermatology 2000; 114: 560568.
40.Chung KM, et al. Antibody recognition of cell surface-associated NS1 triggers Fc-gamma receptor-mediated phagocytosis and clearance of West Nile Virus-infected cells. Journal of Virology 2007; 81: 9551–5.
41.Daffis S, et al. Cell-specific IRF-3 responses protect against West Nile virus infection by interferon-dependent and -independent mechanisms. PLoS Pathogen 2007; 3: e106.
42.Busch MP, et al. Virus and antibody dynamics in acute West Nile virus infection. Journal of Infectious Diseases 2008; 198: 984–93.
43.Tardei G, et al. Evaluation of immunoglobulin M (IgM) and IgG enzyme immunoassays in serologic diagnosis of West Nile virus infection. Journal of Clinical Microbiology 2000; 38: 22322239.
44.Roehrig JT, et al. Persistence of virus-reactive serum immunoglobulin M antibody in confirmed West Nile virus encephalitis cases. Emerging Infectious Diseases 2003; 9: 376379.
45.Kapoor H, et al. Persistence of West Nile virus IgM antibodies in cerebrospinal fluid from patients with CNS disease. Journal of Clinical Virology 2004; 31: 289291.
46.Sambol AR, Hinrichs SH. Evaluation of a new West Nile virus lateral-flow rapid IgM assay. Journal of Virological Methods 2009; 157: 223226.
47.Komar N, Langevan S, Monath TP. Use of a surrogate chimeric virus to detect West Nile virus-neutralizing antibodies in avian and equine sera. Clinical Vaccine Immunology 2009; 16: 134135.
48.Niedrig M, et al. Comparison of ELISA and immunoassays for measurement of IgG and IgM antibody to West Nile virus in human sera against virus neutralisation. Journal of Virological Methods 2007; 139: 103105.
49.Lanciotti RS, et al. Rapid detection of West Nile virus from human clinical specimens, field-collected mosquitoes, and avian samples by a TaqMan reverse transcriptase-PCR assay. Journal of Clinical Microbiology 2000; 38: 40664071.
50.Busch MP, et al. Screening the blood supply for West Nile virus RNA by nucleic acid amplification testing. New England Journal of Medicine 2005; 353: 516517.
51.Tilley PAG, et al. Nucleic acid testing for West Nile virus RNA in plasma enhances rapid diagnosis of acute infection in symptomatic patients. Journal of Infectious Diseases 2006; 193: 13611364.
52.Murray KO, et al. Risk factors for developing encephalitis from West Nile virus infection. Epidemiology and Infection 2006; 134: 13251332.
53.Bode AV, et al. West Nile virus disease: a descriptive study of 228 patients hospitalized in a 4-county region of Colorado in 2003. Clinical Infectious Disease 2006; 42: 12341240.
54.Jean CM et al. 2007: Risk factors for West Nile virus neuroinvasive disease, California. Emerging Infectious Diseases 2005; 13: 19181920.
55.Murray KO, et al. Risk factors for encephalitis from West Nile Virus: a matched case-control study using hospitalized controls. Zoonoses Public Health 2009; 56: 370375.
56.Mateo R, et al. Effects of immunosuppression on West Nile virus infection in hamsters. American Journal of Tropical Medicine and Hygiene 2006; 75: 356362.
57.Kumar D, et al. Community-acquired West Nile virus infection in solid-organ transplant recipients. Transplantation 2004; 77: 399402.
58.Freifeld AG, et al. Seroprevalence of West Nile virus infection in solid organ transplant recipients. Transplant Infectious Disease. Published online: 22 October 2009. doi:10.111/j.1600-6143.2004.00592.x
59.Labowitz Klee A, et al. Long-term prognosis for clinical West Nile virus infection. Emerging Infectious Diseases 2004; 10: 14051411.
60.Gottfried K, Quinn R, Jones T. Clinical description and follow-up investigation of human West Nile virus cases. Southern Medical Journal 2005; 98: 603606.
61.Loeb M, et al. Prognosis after West Nile virus infection. Annals of Internal Medicine 2008; 149: 232241.
62.Cook RL, et al. Demographic and clinical factors associated with persistent symptoms after West Nile virus infection. American Journal of Tropical Medicine and Hygiene 2010; 83: 11331136.
63.Sejvar JJ, et al. West Nile virus-associated flaccid paralysis outcome. Emerging Infectious Diseases 2006; 12: 514516.
64.Murray KO, Resnick M, Miller V. Depression after infection with West Nile virus. Emerging Infectious Diseases 2007; 13: 479481.
65.Pogodina VV, et al. Study on West Nile virus persistence in monkeys. Archives of Virology 1983; 75: 7186.
66.Tesh RB, Xiao SY. Persistence of West Nile Virus infection in vertebrates. In: Diamond MS, ed. West Nile Encephalitis Virus Infection. New York: Springer, 2009, pp. 361377.
67.Siddharthan V, et al. Persistent West Nile virus associated with a neurological sequela in hamsters identified by motor unit number estimation. Journal of Virology. Published online: 18 February 2009. doi:10.1128/JVI.00017-09.
68.Tesh RB, et al. Persistent West Nile virus infection in the golden hamster: studies on its mechanism and possible implications for other flavivirus infections. Journal of Infectious Disease 2005; 192: 287295.
69.Tonry JH, et al. Persistent shedding of West Nile virus in the urine of experimentally infected hamsters. American Journal of Tropical Medicine and Hygiene 2005; 73: 320324.
70.Wu X, et al. Persistent infection and associated nucleotide changes of West Nile virus serially passaged in hamsters. Journal of Genetic Virology 2008; 89: 30733079.
71.Appler KK, et al. Persistence of West Nile virus in the central nervous system and periphery of mice. PLoS ONE 2010; 5:e10649, 112.
72.Murray K, et al. Persistent infection with West Nile virus years after initial infection. Journal of Infectious Disease 2010; 201: 24.
73.Penn RG, et al. Persistent neuroinvasive West Nile virus infection in an immunocompromised patient. Clinical Infectious Disease 2006; 42: 680683.
74.Jordan I, et al. Ribavirin inhibits West Nile virus replication and cytopathic effect in neural cells. Journal of Infectious Disease 2000; 182: 12141217.
75.Enserink M. Infectious disease: West Nile drugs, vaccine still years away. Science 2000; 290: 1483.
76.Anwar A. et al. West Nile premembrane-envelope genetic vaccine encoded as a chimera containing the transmembrane and cytoplasmic domains of a lysosome-associated membrane protein: increased cellular concentration of the transgene product, targeting to the MHC II compartment, and enhanced neutralizing antibody response. Virology 2005; 332: 6677.
77.Maeda A, et al. A PCR-based protocol for the generation of a recombinant West Nile virus. Virus Research 2009; 144: 3543.
78.Monath TP, et al. West Nile virus vaccine. Current Drug Targets – Infectious Disorders 2001; 1: 3750.
79.Guy B, et al. Preclinical and clinical development of YFV 17D-based chimeric vaccines against dengue, West Nile and Japanese encephalitis viruses. Vaccine 2010; 28: 632649.
80.Tesh RB, et al. Immunization with heterologous flavivirus protective against fatal West Nile encephalitis. Emerging Infectious Diseases 2002; 8: 245251.
81.Chung KM, et al. Antibodies against West Nile virus nonstructural protein NS1 prevent lethal infection through Fc gamma receptor-dependent and -independent mechanisms. Journal of Virology 2006; 80: 13401351.
82.Shimoni Z, et al. Treatment of West Nile virus encephalitis with intravenous immunoglobulin. Emerging Infectious Diseases 2001; 7: 759.
83.Hamdan A, et al. Possible benefit of intravenous immunoglobulin therapy in a lung transplant recipient with West Nile encephalitis. Transplant Infectious Disease 2002; 4: 160162.
84.Ben-Nathan D, et al. Using high titer West Nile intravenous immunoglobulin from selected Israeli donors for treatment of West Nile virus infection. BMC Infectious Diseases 2009; 9: 18.
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