Biological Characteristics of West Nile Virus and Its Correlation with the Development of Antiviral Drugs and Vaccines

Diana Nurjanah, N L P I Dharmayanti


West Nile virus (WNV) is a zoonotic RNA virus. Its genome encodes 3 structural and 7 non-structural proteins. Mutations can occur in both structural and non-structural proteins of the virus. Mutations can enhance the pathogenicity and virulence, but some mutations are beneficial for the development of vaccines. Licensed vaccines are only available for horses, while vaccines for humans are still under development. In Indonesia, WNV infection was detected in 2014 in West and East Java, but vaccines and antiviral drugs in both animals and humans are not yet available. This review describe the characteristic of structural and non-structural proteins of WNV and its correlation with mutations and the development of vaccines and antiviral drugs. Molecular identification and further research is needed to predict, prevent and control WNV infections in vectors, susceptible animals and humans.


West Nile virus; zoonotic; mutation; vaccines; antiviral drugs

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Alcalá AC, Hernández-Bravo R, Medina F, Coll DS, Zambrano JL, del Angel RM, Ludert JE. 2017. The dengue virus non-structural protein 1 (NS1) is secreted from infected mosquito cells via a non-classical caveolin-1-dependent pathway. J Gen Virol. 98: 2088–2099.

Alcalá AC, Palomares LA, Ludert JE. 2018. Secretion of nonstructural protein 1 of dengue virus from infected mosquito cells: facts and speculations. J Virol. 92:e00275-18.

Anderson JF, Rahal JJ. 2002. Efficacy of interferon alpha-2b and ribavirin against West Nile virus in vitro. Emerg Infect Dis. 8: 107-108.

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. Virol. 417: 203–210.

Arroyo J, Miller C, Catalan J, Myers GA, Ratterree MS, Trent DW, Monath TP. 2004. ChimeriVax-West Nile Virus live-attenuated vaccine: preclinical evaluation of safety, immunogenicity and efficacy. J Virol. 78: 12497-507.

Barrett ADT. 2018. West Nile in Europe: an increasing public health problem. J Travel Med. 25:1–2.

Barrett PN, Terpening SJ, Snow D, Cobb RR, Kistner O. 2017. Vero cell technology for rapid development of inactivated whole virus vaccines for emerging viral diseases. Expert Rev Vaccines. 16: 883-894.

Bartlow AW, Manore C, Xu C, Kaufeld KA, Del Valle S, Ziemann A, Fairchild G, Fair JM. 2019. Forecasting zoonotic infectious disease response to climate change: mosquito vectors and a changing environment. Vet Sci. 6: 40. DOI: 10.3390 /vetsci6020040

Beasley DWC, Barrett ADT. 2002. Identification of neutralizing epitopes within structural domain iii of the west nile virus envelope protein. J Virol. 76: 13097–13100.

Beasley DWC, Whiteman MC, Zhang S, Huang CY-H, Schneider BS, Smith DR, Gromowski GD, Higgs S, Kinney RM, Barrett ADT. 2005. Envelope protein glycosylation status influences mouse neuroinvasion phenotype of genetic lineage 1 west nile virus strains. J Virol. 79: 8339–8347.

Beloor J, Maes N, Ullah I, Uchil P, Jackson A, Fikrig E, Lee SK, Kumar P. 2018. Small interfering rna-mediated control of virus replication in the cns is therapeutic and enables natural immunity to west nile virus. Cell Host Microbe. 23: 549-556.

Bhuvanakantham R, Chong MK, Ng ML. 2009. Specific interaction of capsid protein and importin-α/β influences West Nile virus production. Biochem Biophys Res Commun. 389: 63–69.

Blázquez AB, Martín-Acebes MA, Saiz J-C. 2016. Inhibition of west nile virus multiplication in cell culture by anti-parkinsonian drugs. Front Microbiol. 7: 296. doi: 10.3389/fmicb.2016.00296

Blazquez AB, Martín-Acebes MA, Saiz JC. 2015. Amino acid substitutions in the non-structural proteins 4A or 4B modulate the induction of autophagy in West Nile virus infected cells independently of the activation of the unfolded protein response. Front Microbiol. 5: 1–9.

Blázquez AB, Vázquez-Calvo Á, Martín-Acebes MA, Saiz JC. 2018. Pharmacological inhibition of protein kinase c reduces West Nile virus replication. Viruses. 10: 91. doi: 10.3390/v10020091

Brandler S, Tangy F. 2013. Vaccines in development against West Nile virus. Viruses. 5: 2384-2409.

Brault AC, Huang CY-H, 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: 1162–1166.

Calvert AE, Huang CY-H, Blair CD, Roehrig JT. 2012. Mutations in the West Nile prM protein affect VLP and virion secretion in vitro. Virol. 433:35–44.

CDC. 2019. Preliminary Maps & Data for 2018 [Internet]. [cited 2019 Sep 5]. Available from:

Chambers T. 1990. Flavivirus genome organization, expression, and replication. Annu Rev Microbiol. 44: 649–688.

Chancey C, Grinev A, Volkova E, Rios M. 2015. The global ecology and epidemiology of West Nile virus. Biomed Res Int. 1–20. /376230

Chang J, Wang L, Ma D, Qu X, Guo H, Xu X, Mason PM, Bourne N, Moriarty R, Gu B, et al. 2009. Novel imino sugar derivatives demonstrate potent antiviral activity against flaviviruses. Antimicrob Agents Chemother. 53: 1501-8.

Chowers MY, Lang R, Nassar F, Ben-David D, Giladi M, Rubinshtein E, Itzhaki A, Mishal J, Siegman-Igra Y, Kitzes R, Pick N, Landau Z, Wolf D, Bin H, Mendelson E, Pitlik SD, Weinberger M. 2001. Clinical characteristics of the West Nile fever outbreak, Israel, 2000. Emerg Infect Dis. 7: 675-678.

Chu J-HJ, Chiang C-CS, Ng M-L. 2007. Immunization of flavivirus West Nile recombinant envelope domain III protein induced specific immune response and protection against West Nile virus infection. J Immunol. 178: 2699-2705.

Colpitts TM, Conway MJ, Montgomery RR, Fikrig E. 2012. West Nile Virus: Biology, Transmission, and Human Infection. Clin Microbiol Rev. 25: 635–648.

Cook S, Holmes EC. 2006. A multigene analysis of the phylogenetic relationships among the flaviviruses (Family: Flaviviridae) and the evolution of vector transmission. Arch Virol. 151: 309-325. doi:10.1007/s00705-005-0626-6

Davis CT, Galbraith SE, Zhang S, Whiteman MC, Li L, Kinney RM, Barrett ADT. 2007. A combination of naturally occurring mutations in North American West Nile Virus nonstructural protein genes and in the 3’ untranslated region alters virus phenotype. J Virol. 81: 6111-6116.

Deas TS, Bennett CJ, Jones SA, Tilgner M, Ren P, Behr MJ, Stein DA, Iversen PL, Kramer LD, Bernard KA, Shi PY. 2007. In vitro resistance selection and in vivo efficacy of morpholino oligomers against west nile virus. Antimicrob Agents Chemother. 51: 2470-2482.

Desprès P, Combredet C, Frenkiel M, Lorin C, Brahic M, Tangy F. 2005. Live Measles Vaccine Expressing the Secreted Form of the West Nile Virus Envelope Glycoprotein Protects against West Nile Virus Encephalitis. J Infect Dis. 191: 207–214.

Diamond MS. 2005. Development of effective therapies against West Nile virus infection. Expert Rev Anti Infect Ther. 3:9 31-44.

Diamond MS. 2009. Progress on the development of therapeutics against West Nile virus. Antiviral Res. 83: 214-27.

Eastwood G, Kramer LD, Goodman SJ, Cunningham AA. 2011. West Nile virus vector competency of Culex quinquefasciatus mosquitoes in the Galápagos Islands. Am J Trop Med Hyg. 85: 426-33.

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: 493-500.

Ebel GD, Fitzpatrick KA, Lim PY, Bennett CJ, Deardorff ER, Jerzak GVS, Kramer LD, Zhou Y, Shi PY, Bernard KA. 2011. Nonconsensus west nile virus genomes arising during mosquito infection suppress pathogenesis and modulate virus fitness in vivo. J Virol. 85: 12605-12613.

Elshuber S. 2003. Cleavage of protein prM is necessary for infection of BHK-21 cells by tick-borne encephalitis virus. J Gen Virol. 84: 183–191.

Escribano-Romero E, Jiménez de Oya N, Domingo E, Saiz JC. 2017. Extinction of West Nile Virus by Favipiravir through Lethal Mutagenesis. Antimicrob Agents Chemother. 61:e01400-17.

Evans JD, Seeger C. 2007. Differential Effects of Mutations in NS4B on West Nile Virus Replication and Inhibition of Interferon Signaling. J Virol. 81: 11809–11816.

Fall G, Di Paola N, Faye M, Dia M, Freire CC de M, Loucoubar C, Zanotto PM de A, Faye O, Sall AA. 2017. Biological and phylogenetic characteristics of West African lineages of West Nile virus. Beasley DWC, editor. PLoS Negl Trop Dis. 11:e0006078.

Ferlenghi I, Clarke M, Ruttan T, Allison SL, Schalich J, Heinz FX, Harrison SC, Rey FA, Fuller SD. 2001. Molecular Organization of a Recombinant Subviral Particle from Tick-Borne Encephalitis Virus. Mol Cell. 7: 593–602.

Fritz R, Blazevic J, Taucher C, Pangerl K, Heinz FX, Stiasny K. 2011. The Unique Transmembrane Hairpin of Flavivirus Fusion Protein E Is Essential for Membrane Fusion. J Virol. 85: 4377–4385.

Gamino V, Höfle U. 2013. Pathology and tissue tropism of natural West Nile virus infection in birds: a review. Vet Res. 44:39.

Gea-Banacloche J, Johnson RT, Bagic A, Butman JA, Murray PR, Agrawal AG. 2004. West Nile virus: pathogenesis and therapeutic options. Ann Intern Med. 140: 545-553.

Di Giallonardo F, Geoghegan JL, Docherty DE, McLean RG, Zody MC, Qu J, Yang X, Birren BW, Malboeuf CM, Newman RM, Ip HS, Holmes EC. 2016. Fluid Spatial Dynamics of West Nile Virus in the United States: Rapid Spread in a Permissive Host Environment. J Virol. 90: 862–872. DOI: 10.1128/JVI.02305-15

Gould LH, Fikrig E. 2004. West Nile virus: a growing concern? J Clin Invest. 113: 1102–1107.

Hall RA, Nisbet DJ, Pham KB, Pyke AT, Smith GA, Khromykh AA. 2003. DNA vaccine coding for the full-length infectious Kunjin virus RNA protects mice against the New York strain of West Nile virus. Proc Natl Acad Sci. 100: 10460-10464. DOI:10.1073/pnas. 1834270100

Hanna SL, Pierson TC, Sanchez MD, Ahmed AA, Murtadha MM, Doms RW. 2005. N-Linked Glycosylation of West Nile Virus Envelope Proteins Influences Particle Assembly and Infectivity. J Virol. 79: 13262–13274.

Hayes EB, Gubler DJ. 2006. West Nile Virus: Epidemiology and Clinical Features of an Emerging Epidemic in the United States. Annu Rev Med. 57: 181–194.

Hughes TP, Paul JH, Smithburn KC, Burke AW. 1940. A neurotropic virus isolated from the blood of a native of uganda. Am J Trop Med Hyg. s1-20: 471-492.

Hunt TA, Urbanowski MD, Kakani K, Law L-MJ, Brinton MA, Hobman TC. 2007. Interactions between the West Nile virus capsid protein and the host cell-encoded phosphatase inhibitor, I 2 PP2A. Cell Microbiol. 9: 2756–2766.

Iglesias MC, Frenkiel MP, Mollier K, Souque P, Despres P, Charneau P. 2006. A single immunization with a minute dose of a lentiviral vector-based vaccine is highly effective at eliciting protective humoral immunity againts West Nile virus. J Gene Med. 8: 265-274.

Iyer A, Kousoulas K. 2013. A Review of Vaccine Approaches for West Nile Virus. Int J Environ Res Public Health. 10: 4200–4223.

Jordan I, Briese T, Fischer N, Lau JY, Lipkin WI. 2000. Ribavirin Inhibits West Nile Virus Replication and Cytopathic Effect in Neural Cells. J Infect Dis. 182: 1214–1217.

Kaiser JA, Barrett ADT. 2019. Twenty Years of Progress Toward West Nile Virus Vaccine Development. Viruses. 11: 823.

Kalil AC, Devetten MP, Singh S, Lesiak B, Poage DP, Bargenquast K, Fayad P, Freifeld AG. 2005. Use of Interferon- in Patients with West Nile Encephalitis: Report of 2 Cases. Clin Infect Dis. 40: 764–766.

Karothia D, Dash PK, Parida M, Bhagyawant S, Kumar JS. 2018. Inhibition of West Nile virus Replication by Bifunctional siRNA Targeting the NS2A and NS5 Conserved Region. Curr Gene Ther. 18: 180–190.

Krishnan M, Garcia-Blanco M. 2014. Targeting Host Factors to Treat West Nile and Dengue Viral Infections. Viruses. 6: 683–708.

Laurent-Rolle M, Boer EF, Lubick KJ, Wolfinbarger JB, Carmody AB, Rockx B, Liu W, Ashour J, Shupert WL, Holbrook MR, et al. 2010. The NS5 Protein of the Virulent West Nile Virus NY99 Strain Is a Potent Antagonist of Type I Interferon-Mediated JAK-STAT Signaling. J Virol. 84: 3503–3515.

Li L, Lok S-M, Yu I-M, Zhang Y, Kuhn RJ, Chen J, Rossmann MG. 2008. The Flavivirus Precursor Membrane-Envelope Protein Complex: Structure and Maturation. Science. 319: 1830–1834.

Li X-F, Deng Y-Q, Yang H-Q, Zhao H, Jiang T, Yu X-D, Li S-H, Ye Q, Zhu S-Y, Wang H-J, et al. 2013. A Chimeric Dengue Virus Vaccine using Japanese Encephalitis Virus Vaccine Strain SA14-14-2 as Backbone Is Immunogenic and Protective against Either Parental Virus in Mice and Nonhuman Primates. J Virol. 87: 13694–13705.

Lim PY, Keating JA, Hoover S, Striker R, Bernard KA. 2011. A thiopurine drug inhibits west nile virus production in cell culture, but not in mice. PLoS One. 6:e26697.

Lim S, Shi P-Y. 2013. West Nile Virus Drug Discovery. Viruses. 5: 2977–3006.

Liu WJ, Wang XJ, Clark DC, Lobigs M, Hall RA, Khromykh AA. 2006. A Single Amino Acid Substitution in the West Nile Virus Nonstructural Protein NS2A Disables Its Ability To Inhibit Alpha/Beta Interferon Induction and Attenuates Virus Virulence in Mice. J Virol. 80: 2396–2404.

Londono-Renteria B, Colpitts TM. 2016. A Brief Review of West Nile Virus Biology. In: Methods Mol Biol. 1435: 1–13.

Lorenz IC, Allison SL, Heinz FX, Helenius A. 2002. Folding and Dimerization of Tick-Borne Encephalitis Virus Envelope Proteins prM and E in the Endoplasmic Reticulum. J Virol. 76: 5480–5491.

Luo Y, Guo X, Yan H, Fang D, Zeng G, Zhou J, Jiang L. 2015. Comprehensive mapping infection-enhancing epitopes of dengue pr protein using polyclonal antibody against prM. Appl Microbiol Biotechnol. 99: 5917-5927.

Lustig Y, Sofer D, Bucris ED, Mendelson E. 2018. Surveillance and Diagnosis of West Nile Virus in the Face of Flavivirus Cross-Reactivity. Front Microbiol. 9: 2421.

Mackenzie JM, Khromykh AA, Parton RG. 2007. Cholesterol Manipulation by West Nile Virus Perturbs the Cellular Immune Response. Cell Host Microbe. 2: 229–239.

MacLachlan NJ, Dubovi EJ, Barthold SW, Swayne DE, Winton JR. 2017. Flaviviridae. In: Fenner’s Vet Virol: Elsevier. 525–545.

van Marle G, Antony J, Ostermann H, Dunham C, Hunt T, Halliday W, Maingat F, Urbanowski MD, Hobman T, Peeling J, Power C. 2007. West Nile Virus-Induced Neuroinflammation: Glial Infection and Capsid Protein-Mediated Neurovirulence. J Virol. 81: 10933-10949.

Martín-Acebes MA. 2012. West Nile virus: A re-emerging pathogen revisited. World J Virol. 1: 51-70.

Martín-Acebes MA, Blázquez AB, Jiménez de Oya N, Escribano-Romero E, Saiz JC. 2011. West nile virus replication requires fatty acid synthesis but is independent on phosphatidylinositol-4-phosphate lipids. PLoS One. 6:e24970.

Martin-Acebes MA, Saiz J-C. 2011. A West Nile virus mutant with increased resistance to acid-induced inactivation. J Gen Virol. 92: 831–840.

Michaelis M, Kleinschmidt MC, Doerr HW, Cinatl J. 2007. Minocycline inhibits West Nile virus replication and apoptosis in human neuronal cells. J Antimicrob Chemother. 60: 981–986.

Monath TP. 2006. Prospects for Development of a Vaccine against the West Nile Virus. Ann N Y Acad Sci. 951: 1–12.

Monath TP, Seligman SJ, Robertson JS, Guy B, Hayes EB, Condit RC, Excler JL, Mac LM, Carbery B, Chen RT. 2015. Live virus vaccines based on a yellow fever vaccine backbone: Standardized template with key considerations for a risk/benefit assessment. Vaccine. 33: 62–72.

Morrey JD, Day CW, Julander JG, Blatt LM, Smee DF, Sidwell RW. 2004. Effect of Interferon-Alpha and Interferon-Inducers on West Nile Virus in Mouse and Hamster Animal Models. Antivir Chem Chemother. 15: 67–75.

Murgue B, Zeller H, Deubel V. 2002. The Ecology and Epidemiology of West Nile Virus in Africa, Europe and Asia. Curr Top Microbiol Immunol. 267: 195–221.

Murray KO, Mertens E, Desprès P. 2010. West Nile virus and its emergence in the United States of America. Vet Res. 41: 67.

Myint KSA, Kosasih H, Artika IM, Perkasa A, Puspita M, Ma’roef CN, Antonjaya U, Ledermann JP, Powers AM, Alisjahbana B. 2014. Short report: West nile virus documented in Indonesia from acute febrile illness specimens. Am J Trop Med Hyg. 90: 260–262.

Nelson S, Jost CA, Xu Q, Ess J, Martin JE, Oliphant T, Whitehead SS, Durbin AP, Graham BS, Diamond MS, Pierson TC. 2008. Maturation of West Nile Virus Modulates Sensitivity to Antibody-Mediated Neutralization.Buchmeier MJ, editor. PLoS Pathog. 4:e1000060.

Nurcahyani D. 2014. 12 Warga Surabaya Terinfeksi Virus West Nile [Internet]. Available from:

Ostlund EN, Crom RL, Pedersen DD, Johnson DJ, Williams WO, Schmitt BJ. 2001. Equine West Nile Encephalitis, United States. Emerg Infect Dis. 7: 665–669.

Pachler K, Lebl K, Berer D, Rudolf I, Hubalek Z, Nowotny N. 2014. Putative New West Nile Virus Lineage in Uranotaenia unguiculata Mosquitoes, Austria, 2013. Emerg Infect Dis. 20: 2119–2122.

Petersen LR, Brault AC, Nasci RS. 2013. West Nile Virus: Review of the Literature. JAMA. 310: 308-315.

Peyre M, Fusheng G, Desvaux S, Roger F. 2009. Avian influenza vaccines: A practical review in relation to their application in the field with a focus on the Asian experience. Epidemiol Infect. 137: 1–21.

Pierce KK, Whitehead SS, Kirkpatrick BD, Grier PL, Jarvis A, Kenney H, Carmolli MP, Reynolds C, Tibery CM, Lovchik J, et al. 2017. A Live Attenuated Chimeric West Nile Virus Vaccine, rWN/DEN4Δ30, Is Well Tolerated and Immunogenic in Flavivirus-Naive Older Adult Volunteers. J Infect Dis. 215: 52–55.

Pletnev AG, Putnak R, Speicher J, Wagar EJ, Vaughn DW. 2002. West Nile virus/dengue type 4 virus chimeras that are reduced in neurovirulence and peripheral virulence without loss of immunogenicity or protective efficacy. Proc Natl Acad Sci. 99: 3036–3041.

Pliego Zamora A, Edmonds JH, Reynolds MJ, Khromykh AA, Ralph SJ. 2016. The in vitro and in vivo antiviral properties of combined monoterpene alcohols against West Nile virus infection. Virology. 495: 18-32.

Pokidysheva E, Zhang Y, Battisti AJ, Bator-Kelly CM, Chipman PR, Xiao C, Gregorio GG, Hendrickson WA, Kuhn RJ, Rossmann MG. 2006. Cryo-EM Reconstruction of Dengue Virus in Complex with the Carbohydrate Recognition Domain of DC-SIGN. Cell. 124: 485–493.

Qiao M, Ashok M, Bernard KA, Palacios G, Zhou ZH, Lipkin WI, Liang TJ. 2004. Induction of Sterilizing Immunity against West Nile Virus (WNV), by Immunization with WNV‐Like Particles Produced in Insect Cells. J Infect Dis. 190: 2104–2108.

Qing M, Yang F, Zhang B, Zou G, Robida JM, Yuan Z, Tang H, Shi PY. 2009. Cyclosporine Inhibits Flavivirus Replication through Blocking the Interaction between Host Cyclophilins and Viral NS5 Protein. Antimicrob Agents Chemother. 53: 3226–3235.

Qing M, Zou G, Wang Q-Y, Xu HY, Dong H, Yuan Z, Shi P-Y. 2010. Characterization of Dengue Virus Resistance to Brequinar in Cell Culture. Antimicrob Agents Chemother. 54: 3686–3695.

Rice CM, Halevy M, Lustig S, Chambers TJ, Nestorowicz A. 1998. West Nile virus envelope proteins: nucleotide sequence analysis of strains differing in mouse neuroinvasiveness. J Gen Virol. 79: 2375–2380.

Rizzoli A, Jiménez-Clavero M, Barzon L, Cordioli P, Figuerola J, Koraka P, Martina B, Moreno A, Nowotny N, Pardigon N, Sanders N, Ulbert S, Tenorio A. 2015. The challenge of West Nile virus in Europe: knowledge gaps and research priorities. Eurosurveillance. 20: 21135.

Rosenberg R, Lindsey NP, Fischer M, Gregory CJ, Hinckley AF, Mead PS, Paz-Bailey G, Waterman SH, Drexler NA, Kersh GJ, et al. 2018. Vital signs: Trends in reported vectorborne disease cases — United States and Territories, 2004-2016. Morb Mortal Wkly Rep. 67: 496-501.

Samuel MA, Diamond MS. 2005. Alpha/Beta Interferon Protects against Lethal West Nile Virus Infection by Restricting Cellular Tropism and Enhancing Neuronal Survival. J Virol. 79: 13350-13361.

Setoh YX, Prow NA, Hobson-Peters J, Lobigs M, Young PR, Khromykh AA, Hall RA. 2012. Identification of residues in West Nile virus pre-membrane protein that influence viral particle secretion and virulence. J Gen Virol. 93: 1965–1975.

Shiryaev SA, Chernov A V., Aleshin AE, Shiryaeva TN, Strongin AY. 2009. NS4A regulates the ATPase activity of the NS3 helicase: A novel cofactor role of the non-structural protein NS4A from West Nile virus. J Gen Virol. 90: 2081-2085.

Siirin MT, Travassos Da Rosa APA, Newman P, Weeks-Levy C, Coller BA, Xiao SY, Lieberman MM, Watts DM. 2008. Evaluation of the efficacy of a recombinant subunit West Nile vaccine in Syrian golden hamsters. Am J Trop Med Hyg. 79: 955-962.

Szentpáli-Gavallér K, Lim S, Dencső L, Bányai K, Koraka P, Osterhaus A, Martina B, Bakonyi T, Bálint Á. 2016. In Vitro and in Vivo Evaluation of Mutations in the NS Region of Lineage 2 West Nile Virus Associated with Neuroinvasiveness in a Mammalian Model. Viruses. 8:49.

Tan TTT, Bhuvanakantham R, Li J, Howe J, Ng M-L. 2009. Tyrosine 78 of premembrane protein is essential for assembly of West Nile virus. J Gen Virol. 90: 1081–1092.

Ulbert S. 2019. West Nile virus vaccines – current situation and future directions. Hum Vaccin Immunother. 15: 2337–2342.

Urbanowski MD, Hobman TC. 2013. The West Nile Virus Capsid Protein Blocks Apoptosis through a Phosphatidylinositol 3-Kinase-Dependent Mechanism. J Virol. 87: 872–881.

Venter M, Steyl J, Human S, Weyer J, Zaayman D, Blumberg L, Leman PA, Paweska J, Swanepoel R. 2010. Transmission of West Nile Virus during Horse Autopsy. Emerg Infect Dis. 16: 573–575.

Wang T, Anderson JF, Magnarelli LA, Bushmich S, Wong S, Koski RA, Fikrig E. 2001. West Nile virus envelope protein: role in diagnosis and immunity. Ann N Y Acad Sci. 951: 325–327.

Whiteman MC, Li L, Wicker JA, Kinney RM, Huang C, Beasley DWC, Chung KM, Diamond MS, Solomon T, Barrett ADT. 2010. Development and characterization of non-glycosylated E and NS1 mutant viruses as a potential candidate vaccine for West Nile virus. Vaccine. 28: 1075–1083.

Whiteman MC, Popov V, Sherman MB, Wen J, Barrett ADT. 2015. Attenuated West Nile Virus Mutant NS1 130-132QQA/175A/207A Exhibits Virus-Induced Ultrastructural Changes and Accumulation of Protein in the Endoplasmic Reticulum. J Virol. 89: 1474-1478.

Wicker JA, Whiteman MC, Beasley DWC, Davis CT, McGee CE, Lee JC, Higgs S, Kinney RM, Huang CYH, Barrett ADT. 2012. Mutational analysis of the West Nile virus NS4B protein. Virology. 426: 22-33.

Wicker JA, Whiteman MC, Beasley DWC, Davis CT, Zhang S, Schneider BS, Higgs S, Kinney RM, Barrett ADT. 2006. A single amino acid substitution in the central portion of the West Nile virus NS4B protein confers a highly attenuated phenotype in mice. Virology. 349: 245-253.

Woods CW, Sanchez AM, Swamy GK, McClain MT, Harrington L, Freeman D, Poore EA, Slifka DK, Poer DeRaad DE, Amanna IJ, et al. 2019. An observer blinded, randomized, placebo-controlled, phase I dose escalation trial to evaluate the safety and immunogenicity of an inactivated West Nile virus Vaccine, HydroVax-001, in healthy adults. Vaccine. 37: 4222–4230.

Yu L, Takeda K, Gao Y. 2017. Characterization of virus-specific vesicles assembled by West Nile virus non-structural proteins. Virology. 506: 130–140.

Zehender G, Veo C, Ebranati E, Carta V, Rovida F, Percivalle E, Moreno A, Lelli D, Calzolari M, Lavazza A, Chiapponi C, Baioni L, Capelli G, Ravagnan S, Da Rold G, Lavezzo E, Palù G, Baldanti F, Barzon L, Galli M. 2017. Reconstructing the recent West Nile virus lineage 2 epidemic in Europe and Italy using discrete and continuous phylogeography. Paraskevis D, editor. PLoS One. 12:e0179679. DOI: 10.1371/journal.pone.0179679

Zhang L, Zhang Z, Weng Z. 2013. Rapid reassortment of internal genes in avian influenza A(H7N9) virus. Clin Infect Dis. 57: 1059–1061.

Zhang S, Li L, Woodson SE, Huang CYH, Kinney RM, Barrett ADT, Beasley DWC. 2006. A mutation in the envelope protein fusion loop attenuates mouse neuroinvasiveness of the NY99 strain of West Nile virus. Virol. 353: 35-40.

Zhang X, Jia R, Shen H, Wang M, Yin Z, Cheng A. 2017. Structures and functions of the envelope glycoprotein in flavivirus infections. Viruses. 9: 338.

Zhang Y. 2003. Structures of immature flavivirus particles. EMBO J. 22: 2604–2613.

Zhang Y, Kaufmann B, Chipman PR, Kuhn RJ, Rossmann MG. 2007. Structure of Immature West Nile Virus. J Virol. 81: 6141–6145.

Zhou Y, Ray D, Zhao Y, Dong H, Ren S, Li Z, Guo Y, Bernard KA, Shi P-Y, Li H. 2007. Structure and Function of Flavivirus NS5 Methyltransferase. J Virol. 81: 3891-903.

Zohaib A, Niazi SK, Saqib M, Sajid MS, Khan I, Sial A-R, Athar MA, Taj Z, Abbas G, Rathore MA, et al. 2019. Detection of West Nile virus lineage 1 sequences in blood donors, Punjab Province, Pakistan. Int J Infect Dis. 81: 137–139.

Zou G, Zhang B, Lim P-Y, Yuan Z, Bernard KA, Shi P-Y. 2009. Exclusion of West Nile Virus Superinfection through RNA Replication. J Virol. 83: 11765–11776.

Zybert IA, van der Ende-Metselaar H, Wilschut J, Smit JM. 2008. Functional importance of dengue virus maturation: Infectious properties of immature virions. J Gen Virol. 89: 3047-3051


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