Rational Design of a Flavivirus Vaccine by Abolishing Viral RNA 2 '-O Methylation
文献类型：期刊论文
| 作者 | Li, Shi-Hua2,3; Dong, Hongping4; Li, Xiao-Feng2,3; Xie, Xuping4; Zhao, Hui2,3; Deng, Yong-Qiang2,3; Wang, Xiao-Yu2,5; Ye, Qing2,3; Zhu, Shun-Ya2,3; Wang, Hong-Jiang2,3 |
| 刊名 | JOURNAL OF VIROLOGY
 |
| 出版日期 | 2013-05-01 |
| 卷号 | 87期号:10页码:5812-5819 |
| ISSN号 | 0022-538X |
| DOI | 10.1128/JVI.02806-12 |
| 英文摘要 | Viruses that replicate in the cytoplasm cannot access the host nuclear capping machinery. These viruses have evolved viral methyltransferase(s) to methylate N-7 and 2'-O cap of their RNA; alternatively, they "snatch" host mRNA cap to form the 5' end of viral RNA. The function of 2'-O methylation of viral RNA cap is to mimic cellular mRNA and to evade host innate immune restriction. A cytoplasmic virus defective in 2'-O methylation is replicative, but its viral RNA lacks 2'-O methylation and is recognized and eliminated by the host immune response. Such a mutant virus could be rationally designed as a live attenuated vaccine. Here, we use Japanese encephalitis virus (JEV), an important mosquito-borne flavivirus, to prove this novel vaccine concept. We show that JEV methyltransferase is responsible for both N-7 and 2'-O cap methylations as well as evasion of host innate immune response. Recombinant virus completely defective in 2'-O methylation was stable in cell culture after being passaged for >30 days. The mutant virus was attenuated in mice, elicited robust humoral and cellular immune responses, and retained the engineered mutation in vivo. A single dose of immunization induced full protection against lethal challenge with JEV strains in mice. Mechanistically, the attenuation phenotype was attributed to the enhanced sensitivity of the mutant virus to the antiviral effects of interferon and IFIT proteins. Collectively, the results demonstrate the feasibility of using 2'-O methylation-defective virus as a vaccine approach; this vaccine approach should be applicable to other flaviviruses and nonflaviviruses that encode their own viral 2'-O methyltransferases. |
| 资助项目 | Basic Research Project of China[2012CB518904] ; National Natural Science Foundation of China[81101243] ; National Natural Science Foundation of China[31270974] ; TCR flagship STOP Dengue program from the National Medical Research Council in Singapore ; Beijing Nova Program of Science and Technology[2010B041] |
| WOS研究方向 | Virology |
| 语种 | 英语 |
| WOS记录号 | WOS:000318155000042 |
| 出版者 | AMER SOC MICROBIOLOGY |
| 源URL | [http://202.127.146.157/handle/2RYDP1HH/3848]  |
| 专题 | 中国科学院武汉植物园 |
| 通讯作者 | Qin, Cheng-Feng |
| 作者单位 | 1.ASTAR, Singapore Immunol Network, Singapore, Singapore 2.Beijing Inst Microbiol & Epidemiol, Dept Virol, Beijing, Peoples R China 3.State Key Lab Pathogen & Biosecur, Beijing, Peoples R China 4.Novartis Inst Trop Dis, Singapore, Singapore 5.Zhejiang Univ, Ctr Biomat & Biopathways, Dept Chem, Hangzhou 310003, Zhejiang, Peoples R China 6.Chinese Acad Sci, State Key Lab Virol, Wuhan Inst Virol, Wuhan, Peoples R China 7.Chinese Acad Sci, Shanghai Inst Pasteur, Shanghai, Peoples R China |
| 推荐引用方式 GB/T 7714 | Li, Shi-Hua,Dong, Hongping,Li, Xiao-Feng,et al. Rational Design of a Flavivirus Vaccine by Abolishing Viral RNA 2 '-O Methylation[J]. JOURNAL OF VIROLOGY,2013,87(10):5812-5819. |
| APA | Li, Shi-Hua.,Dong, Hongping.,Li, Xiao-Feng.,Xie, Xuping.,Zhao, Hui.,...&Shi, Pei-Yong.(2013).Rational Design of a Flavivirus Vaccine by Abolishing Viral RNA 2 '-O Methylation.JOURNAL OF VIROLOGY,87(10),5812-5819. |
| MLA | Li, Shi-Hua,et al."Rational Design of a Flavivirus Vaccine by Abolishing Viral RNA 2 '-O Methylation".JOURNAL OF VIROLOGY 87.10(2013):5812-5819. |
入库方式： OAI收割
来源：武汉植物园
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