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

39 Citations (Scopus)

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

Fingerprint

West Nile virus
Replicon
RNA
Viruses
Mutation
Tail
Flavivirus
Inbred C3H Mouse
Mutant Proteins
Culicidae
Endoplasmic Reticulum
Interferons
Rodentia
Cell Culture Techniques
Phenotype
Membranes
Growth
Genes

Keywords

  • Flavivirus replication
  • NS4B
  • West Nile virus

ASJC Scopus subject areas

  • Virology
  • Infectious Diseases

Cite this

Puig-Basagoiti, F., Tilgner, M., Bennett, C. J., Zhou, Y., Muñoz-Jordán, J. L., García-Sastre, 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

A mouse cell-adapted NS4B mutation attenuates West Nile virus RNA synthesis. / Puig-Basagoiti, Francesc; Tilgner, Mark; Bennett, Corey J.; Zhou, Yangsheng; Muñoz-Jordán, Jorge L.; García-Sastre, Adolfo; Bernard, Kristen A.; Shi, Pei-Yong.

In: Virology, Vol. 361, No. 1, 25.04.2007, p. 229-241.

Research output: Contribution to journalArticle

Puig-Basagoiti, F, Tilgner, M, Bennett, CJ, Zhou, Y, Muñoz-Jordán, JL, García-Sastre, A, Bernard, KA & Shi, P-Y 2007, 'A mouse cell-adapted NS4B mutation attenuates West Nile virus RNA synthesis', Virology, vol. 361, no. 1, pp. 229-241. https://doi.org/10.1016/j.virol.2006.11.012
Puig-Basagoiti F, Tilgner M, Bennett CJ, Zhou Y, Muñoz-Jordán JL, García-Sastre A et al. A mouse cell-adapted NS4B mutation attenuates West Nile virus RNA synthesis. Virology. 2007 Apr 25;361(1):229-241. https://doi.org/10.1016/j.virol.2006.11.012
Puig-Basagoiti, Francesc ; Tilgner, Mark ; Bennett, Corey J. ; Zhou, Yangsheng ; Muñoz-Jordán, Jorge L. ; García-Sastre, Adolfo ; Bernard, Kristen A. ; Shi, Pei-Yong. / A mouse cell-adapted NS4B mutation attenuates West Nile virus RNA synthesis. In: Virology. 2007 ; Vol. 361, No. 1. pp. 229-241.
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