Critical role of Dengue Virus NS1 protein in viral replication
10.1007/s12250-014-3459-1
- Author:
Jingjing FAN
;
Yi LIU
;
Zhiming YUAN
- Publication Type:Journal Article
- Keywords:
dengue type 2 virus;
NS1;
replication;
glycosylation site
- From:
Virologica Sinica
2014;(3):162-169
- CountryChina
- Language:Chinese
-
Abstract:
Dengue virus (DENV) nonstructural protein 1 (NS1) is a highly conserved 46-kDa protein that contains 2 glycosylation sites (Asn-130 and Asn-207) and 12 conserved cysteine (Cys) residues. Here, we performed site-directed mutagenesis to generate systematic mutants of viral strain TSV01. The results of the subsequent analysis showed that an alanine substitution at the second N-linked glycan Asn-207 in NS1 delayed viral RNA synthesis, reduced virus plaque size, and weakened the cytopathic effect. Three mutants at Cys sites (Cys-4, Cys-55, Cys-291) and a C-terminal deletion (ΔC) mutant signiifcantly impaired RNA synthesis, and consequently abolished viral growth, whereas alanine mutations at Asn-130 and Glu-173 resulted in phenotypes that were similar to the wild-type (WT) virus. Further analysis showed that the Asn-207 mutation slightly delayed viral replication. These results suggest that the three conserved disulifde bonds and the second N-linked glycan in NS1 are required for DENV-2 replication.