title: West Nile 25A virus infection of B-cell-deficient ((micro)MT) mice: characterization of neuroinvasiveness and pseudoreversion of the viral envelope protein.
abstract: The attenuated West Nile virus 25A strain (WN25A) was investigated for its neuroinvasive properties in B-cell-deficient (microMT) mice. After peripheral inoculation, WN25A caused fatal encephalitis in the majority of 6-8-week-old mice, characterized by a systemic infection with viraemia, moderate virus burdens in peripheral tissues and a high titre of brain-associated virus. Mice generally succumbed to infection within a few weeks of infection. However, others survived for as long as 10 weeks, and some for even longer. Normal age-matched C57BL/6 mice showed no signs of illness after inoculation with WN25A virus. Nucleotide sequencing of WN25A viruses recovered from the brains of B-cell-deficient mice revealed that the conserved N-linked glycosylation site in the viral envelope protein was abolished by substitution of a serine residue at position 155. This was found to be a pseudoreversion relative to the wild-type WN-Israel strain, based on virulence testing of one such brain-associated virus in both B-cell-deficient and normal C57BL/6 mice. This study provides further characterization of the mouse virulence properties of the attenuated WN25A virus in the context of B-cell deficiency. Replication in these mice does not involve rapid neuroadaptation or reversion of WN25A virus to a neuroinvasive phenotype. Molecular modelling studies suggest a difference in local structure of the E protein associated with either an asparagine or serine residue at position 155 compared with the tyrosine found in the virulent parental WN-Israel virus.
authors.affiliation: Department of Molecular Microbiology and Immunology, Saint Louis University School of Medicine, 1402 South Grand Ave, St Louis, MO 63104, USA.
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Chambers
authors.affiliation: Department of Molecular Microbiology and Immunology, Saint Louis University School of Medicine, 1402 South Grand Ave, St Louis, MO 63104, USA.
authors.forename: Deborah A
authors.initials: DA
authors.lastname: Droll
authors.affiliation: Department of Molecular Microbiology and Immunology, Saint Louis University School of Medicine, 1402 South Grand Ave, St Louis, MO 63104, USA.
authors.forename: Andrew H
authors.initials: AH
authors.lastname: Walton
authors.affiliation: Department of Molecular Microbiology and Immunology, Saint Louis University School of Medicine, 1402 South Grand Ave, St Louis, MO 63104, USA.
authors.forename: Julie
authors.initials: J
authors.lastname: Schwartz
authors.affiliation: Department of Molecular Microbiology and Immunology, Saint Louis University School of Medicine, 1402 South Grand Ave, St Louis, MO 63104, USA.
authors.forename: William S M
authors.initials: WSM
authors.lastname: Wold
authors.affiliation: Department of Molecular Microbiology and Immunology, Saint Louis University School of Medicine, 1402 South Grand Ave, St Louis, MO 63104, USA.
authors.forename: Janice
authors.initials: J
authors.lastname: Nickells
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology / Q000473:pathology; D001921:Brain / Q000821:virology*; D002522:Chlorocebus aethiops; D004195:Disease Models, Animal; D018792:Encephalitis, Viral / Q000276:immunology / Q000401:mortality / Q000473:pathology / Q000821:virology; D006031:Glycosylation; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009154:Mutation; D017422:Sequence Analysis, DNA; D014709:Vero Cells; D014759:Viral Envelope Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D014766:Viremia / Q000276:immunology / Q000401:mortality / Q000473:pathology / Q000821:virology; D014774:Virulence; D014901:West Nile Fever / Q000276:immunology / Q000401:mortality / Q000473:pathology / Q000821:virology; D014902:West Nile virus / Q000235:genetics / Q000378:metabolism / Q000472:pathogenicity*
chemical_list: D014759:Viral Envelope Proteins