A mouse cell-adapted NS4B mutation attenuates West Nile virus RNA synthesis

Francesc Puig-Basagoiti, Mark Tilgner, Corey J. Bennett, Yangsheng Zhou, Jorge L. Muñoz-Jordán, Adolfo García-Sastre, Kristen A. Bernard, Pei Yong Shi

Research output: Contribution to journalArticle

41 Scopus citations

Abstract

An adaptive mutation (E249G) within West Nile virus (WNV) NS4B gene was consistently recovered from replicon RNAs in C3H/He mouse cells. The E249G is located at the C-terminal tail of NS4B predicted to be on the cytoplasmic side of the endoplasmic reticulum membrane. The E249G substitution reduced replicon RNA synthesis. Compared with the wild-type NS4B, the E249G mutant protein exhibited a similar efficiency in evasion of interferon-β response. Recombinant E249G virus exhibited smaller plaques, slower growth kinetics, and lower RNA synthesis than the wild-type virus in a host-dependent manner, with the greatest difference in rodent cells (C3H/He and BHK-21) and the least difference in mosquito cells (C3/36). Selection of revertants of E249G virus identified a second site mutation at residue 246, which could compensate for the low replication phenotype in cell culture. These results demonstrate that distinct residues within the C-terminal tail of flavivirus NS4B are critical for viral replication.

Original languageEnglish (US)
Pages (from-to)229-241
Number of pages13
JournalVirology
Volume361
Issue number1
DOIs
StatePublished - Apr 25 2007
Externally publishedYes

Keywords

  • Flavivirus replication
  • NS4B
  • West Nile virus

ASJC Scopus subject areas

  • Virology

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  • Cite this

    Puig-Basagoiti, F., Tilgner, M., Bennett, C. J., Zhou, Y., Muñoz-Jordán, J. L., García-Sastre, A., Bernard, K. A., & Shi, P. Y. (2007). A mouse cell-adapted NS4B mutation attenuates West Nile virus RNA synthesis. Virology, 361(1), 229-241. https://doi.org/10.1016/j.virol.2006.11.012