%0 Journal Article %A Chambers, Thomas J. %A Droll, Deborah A. %A Walton, Andrew H. %A Schwartz, Julie %A Wold, William S. M. %A Nickells, Janice %T West Nile 25A virus infection of B-cell-deficient (μMT) mice: characterization of neuroinvasiveness and pseudoreversion of the viral envelope protein %D 2008 %J Journal of General Virology, %V 89 %N 3 %P 627-635 %@ 1465-2099 %R https://doi.org/10.1099/vir.0.83297-0 %I Microbiology Society, %X The attenuated West Nile virus 25A strain (WN25A) was investigated for its neuroinvasive properties in B-cell-deficient (μMT) 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. %U https://www.microbiologyresearch.org/content/journal/jgv/10.1099/vir.0.83297-0