• 1.

    Takasaki T, 2007. West Nile fever/encephalitis. Uirusu 57: 199205.

  • 2.

    Hamman MH, Delphine HC, Winston HP, 1965. Antigenic variation of West Nile virus in relation to geography. Am J Epidemiol 82: 4055.

  • 3.

    Hubálek Z, Halouzka J, 1999. West Nile fever—a reemerging mosquito-borne viral disease in Europe. Emerg Infect Dis 5: 643650.

  • 4.

    Anderson JF, Vossbrinck CR, Andreadis TG, Iton A, Beckwith WH 3rd, Mayo DR, 2001. A phylogenetic approach to following West Nile virus in Connecticut. Proc Natl Acad Sci USA 98: 1288512889.

    • Search Google Scholar
    • Export Citation
  • 5.

    Garmendia AE, Van Kruiningen HJ, French RA, 2001. The West Nile virus: its recent emergence in North America. Microbes Infect 3: 223229.

  • 6.

    Marfin AA, Gubler DJ, 2001. West Nile encephalitis: an emerging disease in the United States. Clin Infect Dis 33: 17131719.

  • 7.

    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.

    • Search Google Scholar
    • Export Citation
  • 8.

    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.

    • Search Google Scholar
    • Export Citation
  • 9.

    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: 311322.

    • Search Google Scholar
    • Export Citation
  • 10.

    Seligman SJ, Bucher DJ, 2003. The importance of being outer: consequences of the distinction between the outer and inner surfaces of flavivirus glycoprotein E. Trends Microbiol 11: 108110.

    • Search Google Scholar
    • Export Citation
  • 11.

    Chambers TJ, Hahn CS, Galler R, Rice CM, 1990. Flavivirus genome organization, expression, and replication. Annu Rev Microbiol 44: 649688.

  • 12.

    Shirato K, Miyoshi H, Goto A, Ako Y, Ueki T, Kariwa H, Takashima I, 2004. Viral envelope protein glycosylation is a molecular determinant of the neuroinvasiveness of the New York strain of West Nile virus. J Gen Virol 85: 36373645.

    • Search Google Scholar
    • Export Citation
  • 13.

    Goto A, Yoshii K, Obara M, Ueki T, Mizutani T, Kariwa H, Takashima I, 2005. Role of the N-linked glycans of the prM and E envelope proteins in tick-borne encephalitis virus particle secretion. Vaccine 23: 30433052.

    • Search Google Scholar
    • Export Citation
  • 14.

    Beasley DW, Whiteman MC, Zhang S, Huang CY, Schneider BS, Smith DR, Gromowski GD, Higgs S, Kinney RM, Barrett AD, 2005. Envelope protein glycosylation status influences mouse neuroinvasion phenotype of genetic lineage 1 West Nile virus strains. J Virol 79: 83398347.

    • Search Google Scholar
    • Export Citation
  • 15.

    Maeda A, Murata R, Akiyama M, Takashima I, Kariwa H, Watanabe T, Kurane I, Maeda J, 2009. A PCR-based protocol for generating of a recombinant West Nile virus. Virus Res 144: 3543.

    • Search Google Scholar
    • Export Citation
  • 16.

    Peiris JS, Porterfield JS, Roehrig JT, 1982. Monoclonal antibodies against the flavivirus West Nile. J Gen Virol 58: 283289.

  • 17.

    Komoro K, Hayasaka D, Mizutani T, Kariwa H, Takashima I, 2000. Characterization of monoclonal antibodies against Hokkaido strain tick-borne encephalitis virus. Microbiol Immunol 44: 533536.

    • Search Google Scholar
    • Export Citation
  • 18.

    Beasley DW, Davis CT, Estrada-Franco J, Navarro-Lopez R, Campomanes-Cortes A, Tesh RB, Weaver SC, Barrett AD, 2004. Genome sequence and attenuating mutations in West Nile virus isolate from Mexico. Emerg Infect Dis 10: 22212224.

    • Search Google Scholar
    • Export Citation
  • 19.

    Halevy M, Akov Y, Ben-Nathan D, Kobiler D, Lachmi B, Lustig S, 1994. Loss of active neuroinvasiveness in attenuated strains of West Nile virus: pathogenicity in immunocompetent and SCID mice. Arch Virol 137: 355370.

    • Search Google Scholar
    • Export Citation
  • 20.

    Moudy RM, Zhang B, Shi PY, Kramer LD, 2009. West Nile virus envelope protein glycosylation is required for efficient viral transmission by Culex vectors. Virology 387: 222228.

    • Search Google Scholar
    • Export Citation
  • 21.

    Gibbs SE, Ellis AE, Mead DG, Allison AB, Moulton JK, Howerth EW, Stallknecht DE, 2005. West Nile virus detection in the organs of naturally infected blue jays (Cyanocitta cristata). J Wildl Dis 41: 354362.

    • Search Google Scholar
    • Export Citation
  • 22.

    Kasturi L, Eshleman JR, Wunner WH, Shakin-Eshleman SH, 1995. The hydroxy amino acid in an Asn-X-Ser/Thr sequon can influence N-linked core glycosylation efficiency and the level of expression of a cell surface glycoprotein. J Biol Chem 270: 1475614761.

    • Search Google Scholar
    • Export Citation
  • 23.

    Wicker JA, Whiteman MC, Beasley DW, Davis CT, Zhang S, Schneider BS, Higgs S, Kinney RM, Barrett AD, 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: 245253.

    • Search Google Scholar
    • Export Citation
  • 24.

    Kinney RM, Huang CY, Whiteman MC, Bowen RA, Langevin SA, Miller BR, Brault AC, 2006. Avian virulence and thermostable replication of the North American strain of West Nile virus. J Gen Virol 87: 36113622.

    • Search Google Scholar
    • Export Citation
  • 25.

    Jia Y, Moudy RM, Dupuis AP 2nd, Ngo KA, Maffei JG, Jerzak GV, Franke MA, Kauffman EB, Kramer LD, 2007. Characterization of a small plaque variant of West Nile virus isolated in New York in 2000. Virology 367: 339347.

    • Search Google Scholar
    • Export Citation
  • 26.

    Rey FA, Heinz FX, Mandl C, Kunz C, Harrison SC, 1995. The envelope glycoprotein from tick-borne encephalitis virus at 2 A resolution. Nature 375: 291298.

    • Search Google Scholar
    • Export Citation
  • 27.

    Modis Y, Ogata S, Clements D, Harrison SC, 2003. A ligand-binding pocket in the dengue virus envelope glycoprotein. Proc Natl Acad Sci USA 100: 69866991.

    • Search Google Scholar
    • Export Citation

 

 

 

 

Glycosylation of the West Nile Virus Envelope Protein Increases In Vivo and In Vitro Viral Multiplication in Birds

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  • 1 Laboratory of Public Health, Department of Environmental Veterinary Sciences, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo, Hokkaido, Japan; Department of Infectious Disease Control, Faculty of Medicine, Oita University, Oita, Japan; Department of Prion Diseases, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo, Hokkaido, Japan; Laboratory of Comparative Pathology, Department of Veterinary Clinical Sciences, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo, Hokkaido, Japan

Many West Nile (WN) virus isolates associated with significant outbreaks possess a glycosylation site on the envelope (E) protein. E-protein glycosylated variants of New York (NY) strains of WN virus are more neuroinvasive in mice than the non-glycosylated variants. To determine how E protein glycosylation affects the interactions between WN virus and avian hosts, we inoculated young chicks with NY strains of WN virus containing either glycosylated or non-glycosylated variants of the E protein. The glycosylated variants were more virulent and had higher viremic levels than the non-glycosylated variants. The glycosylation status of the variant did not affect viral multiplication and dissemination in mosquitoes in vivo. Glycosylated variants showed more heat-stable propagation than non-glycosylated variants in mammalian (BHK) and avian (QT6) cells but not in mosquito (C6/36) cells. Thus, E-protein glycosylation may be a requirement for efficient transmission of WN virus from avian hosts to mosquito vectors.

Author Notes

*Address correspondence to Ikuo Takashima, Laboratory of Public Health, Department of Environmental Veterinary Sciences, Graduate School of Veterinary Medicine, Hokkaido University, kita-18 nishi-9, kita-ku, Sapporo, Hokkaido 060-0818, Japan. E-mail: takasima@vetmed.hokudai.ac.jp

Authors' addresses: Ryo Murata, Junko Maeda, Kentaro Yoshii, Hiroaki Kariwa, and Ikuo Takashima, Laboratory of Public Health, Department of Environmental Veterinary Sciences, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo, Hokkaido, Japan, E-mails: murata-r@vetmed.hokudai.ac.jp, jimaeda@vetmed.hokudai.ac.jp, kyoshii@vetmed.hokudai.ac.jp, kariwa@vetmed.hokudai.ac.jp, and takasima@vetmed.hokudai.ac.jp. Yuki Eshita, Department of Infectious Disease Control, Faculty of Medicine, Oita University, Hasama-machi, Yufu-shi, Oita, Japan, E-mail: yeshita@med.oita-u.ac.jp. Akihiko Maeda, Department of Prion Diseases, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo, Japan, E-mail: amaeda@vetmed.hokudai.ac.jp. Saki Akita, Tomohisa Tanaka, and Takashi Umemura, Laboratory of Comparative Pathology, Department of Veterinary Clinical Sciences, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo, Hokkaido, Japan, E-mails: s36040002j@ec.hokudai.ac.jp, t-tanaka@vetmed.hokudai.ac.jp, and umemura@vetmed.hokudai.ac.jp.

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