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A mouse cell-adapted NS4B mutation attenuates West Nile virus RNA synthesis
- Source :
-
Virology . Apr2007, Vol. 361 Issue 1, p229-241. 13p. - Publication Year :
- 2007
-
Abstract
- 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. [Copyright &y& Elsevier]
- Subjects :
- *VIRAL replication
*WEST Nile virus
*GENETIC mutation
*GENETIC load
Subjects
Details
- Language :
- English
- ISSN :
- 00426822
- Volume :
- 361
- Issue :
- 1
- Database :
- Academic Search Index
- Journal :
- Virology
- Publication Type :
- Academic Journal
- Accession number :
- 24697171
- Full Text :
- https://doi.org/10.1016/j.virol.2006.11.012