{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T21:31:19Z","timestamp":1791235879606,"version":"4.1.0"},"reference-count":37,"publisher":"Microbiology Society","issue":"7","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2011,7,1]]},"abstract":"<jats:p>Our previous studies have shown that the Japanese encephalitis virus (JEV) strain Mie\/40\/2004 is the most virulent of the strains isolated by us in Japan from 2002 to 2004. Comparison of the amino acid sequence of Mie\/40\/2004 with those of low-virulence strains revealed that an isoleucine residue at position 3 of the Mie\/40\/2004 NS4A protein may increase viral pathogenicity. A recombinant virus with a single valine-to-isoleucine substitution (V3I) at position 3 in the low-virulence Mie\/41\/2002 background (rJEV-Mie41-NS4A<jats:sup>V3I<\/jats:sup>) exhibited increased virulence in mice compared with the Mie\/41\/2002 parent strain. The V3I mutation did not affect virus growth in several cell lines. These results demonstrate that the isoleucine at position 3 in the NS4A protein of Mie\/40\/2004 is responsible for its high virulence <jats:italic>in vivo<\/jats:italic>. This is the first report to show that an amino acid substitution in a flavivirus NS4A protein alters viral pathogenicity in mice.<\/jats:p>","DOI":"10.1099\/vir.0.031237-0","type":"journal-article","created":{"date-parts":[[2011,3,17]],"date-time":"2011-03-17T00:55:52Z","timestamp":1300323352000},"page":"1601-1606","source":"Crossref","is-referenced-by-count":13,"title":["An amino acid substitution (V3I) in the Japanese encephalitis virus NS4A protein increases its virulence in mice, but not its growth rate in vitro"],"prefix":"10.1099","volume":"92","author":[{"given":"Yukie","family":"Yamaguchi","sequence":"first","affiliation":[{"name":"Department of Pathology, Immunology and Microbiology, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo, Tokyo 113-0033, Japan"},{"name":"Department of Virology 1, National Institute of Infectious Diseases, 1-23-1 Toyama, Shinjuku, Tokyo 162-8640, 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