A single amino acid in nonstructural protein ns4b confers virulence to dengue virus in ag129 mice through enhancement of viral rna synthesis
文献类型：期刊论文
| 作者 | Grant, Dixon1,2; Tan, Grace K.3; Qing, Min1,4; Ng, Jowin K. W.3; Yip, Andy1; Zou, Gang1; Xie, Xuping1,4; Yuan, Zhiming4; Schreiber, Mark J.1; Schul, Wouter1 |
| 刊名 | Journal of virology
 |
| 出版日期 | 2011-08-01 |
| 卷号 | 85期号:15页码:7775-7787 |
| ISSN号 | 0022-538X |
| DOI | 10.1128/jvi.00665-11 |
| 通讯作者 | Alonso, sylvie(micas@nus.edu.sg) |
| 英文摘要 | Dengue (den) is a mosquito-borne viral disease that has become an increasing economic and health burden for the tropical and subtropical world. the lack of an appropriate animal model of den has greatly impeded the study of its pathogenesis and the development of vaccines/antivirals. we recently reported a den virus 2 (denv-2) strain (d2y98p) that lethally infects immunocompromised ag129 mice, resulting in organ damage or dysfunction and increased vascular permeability, hallmarks of severe den in patients (g. k. tan et al., plos negl. trop. dis. 4:e672, 2010). here we report the identification of one critical virulence determinant of strain d2y98p. by mutagenesis, we showed that a phe-to-leu alteration at amino acid position 52 in nonstructural protein ns4b completely abolished the pathogenicity of the d2y98p virus, as evidenced by a lack of lethality and the absence of histological signs of disease, which correlated with reduced viral titers and intact vascular permeability. conversely, a leu-to-phe alteration at position 52 of ns4b in nonvirulent denv-2 strain tsv01 led to 80% lethality and increased viremia. the ns4b(phe52) viruses displayed enhanced rna synthesis in mammalian cells but not in mosquito cells. the increased viral rna synthesis was independent of the ability of ns4b to interfere with the host type i interferon response. overall, our results demonstrate that phe at position 52 in ns4b confers virulence in mice on two independent denv-2 strains through enhancement of viral rna synthesis. in addition to providing further insights into the functional role of ns4b protein, our findings further support a direct relationship between viral loads and den pathogenesis in vivo, consistent with observations in den patients. |
| WOS关键词 | WEST-NILE-VIRUS ; VACCINE CANDIDATE ; HEMORRHAGIC-FEVER ; 3'-UNTRANSLATED REGION ; MOUSE NEUROVIRULENCE ; DISEASE SEVERITY ; NS5 PROTEIN ; LENGTH CDNA ; INTERFERON ; STRAIN |
| WOS研究方向 | Virology |
| WOS类目 | Virology |
| 语种 | 英语 |
| WOS记录号 | WOS:000292447300029 |
| 出版者 | AMER SOC MICROBIOLOGY |
| URI标识 | http://www.irgrid.ac.cn/handle/1471x/2375933 |
| 专题 | 武汉病毒研究所 |
| 通讯作者 | Alonso, Sylvie |
| 作者单位 | 1.Novartis Inst Trop Dis, Singapore, Singapore 2.Duke Natl Univ Singapore, Grad Sch Med, Singapore, Singapore 3.Natl Univ Singapore, Immunol Programme, Dept Microbiol, Singapore 117548, Singapore 4.Chinese Acad Sci, Wuhan Inst Virol, State Key Lab Virol, Beijing 100864, Peoples R China |
| 推荐引用方式 GB/T 7714 | Grant, Dixon,Tan, Grace K.,Qing, Min,et al. A single amino acid in nonstructural protein ns4b confers virulence to dengue virus in ag129 mice through enhancement of viral rna synthesis[J]. Journal of virology,2011,85(15):7775-7787. |
| APA | Grant, Dixon.,Tan, Grace K..,Qing, Min.,Ng, Jowin K. W..,Yip, Andy.,...&Alonso, Sylvie.(2011).A single amino acid in nonstructural protein ns4b confers virulence to dengue virus in ag129 mice through enhancement of viral rna synthesis.Journal of virology,85(15),7775-7787. |
| MLA | Grant, Dixon,et al."A single amino acid in nonstructural protein ns4b confers virulence to dengue virus in ag129 mice through enhancement of viral rna synthesis".Journal of virology 85.15(2011):7775-7787. |
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来源：武汉病毒研究所
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