HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Chambers, T. J. Articles by Nickells, J. Search for Related Content PubMed PubMed Citation Articles by Chambers, T. J. Articles by Nickells, J. Agricola Articles by Chambers, T. J. Articles by Nickells, J.

West Nile 25A virus infection of B-cell-deficient (µMT) mice: characterization of neuroinvasiveness and pseudoreversion of the viral envelope protein

Department of Molecular Microbiology and Immunology, Saint Louis University School of Medicine, 1402 South Grand Ave, St Louis, MO 63104, USA

Correspondence
Thomas J. Chambers
thomas_chambers2{at}merck.com

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.

The GenBank/EMBL/DDBJ accession numbers for the brain-associated viral variants are EU391638–EU391642.