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Critical role of Dengue Virus NS1 protein in viral replication

  • Research Article
  • Published:
Virologica Sinica

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 significantly 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 disulfide bonds and the second N-linked glycan in NS1 are required for DENV-2 replication.

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Authors and Affiliations

  1. Key Laboratory of Agricultural and Environmental Microbiology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, 430071, China

    Jingjing Fan, Yi Liu & Zhiming Yuan

  2. University of the Chinese Academy of Sciences, Beijing, 100039, China

    Jingjing Fan & Yi Liu

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  1. Jingjing Fan
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  2. Yi Liu
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  3. Zhiming Yuan
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Correspondence to Zhiming Yuan.

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Fan, J., Liu, Y. & Yuan, Z. Critical role of Dengue Virus NS1 protein in viral replication. Virol. Sin. 29, 162–169 (2014). https://doi.org/10.1007/s12250-014-3459-1

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  • DOI: https://doi.org/10.1007/s12250-014-3459-1

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