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塞姆利基森林病毒基因组的操作及其在疫苗构建中的潜力。

Manipulation of the Semliki Forest virus genome and its potential for vaccine construction.

作者信息

Atkins G J, Sheahan B J, Liljeström P

机构信息

Department of Microbiology, Trinity College, Dublin, Ireland.

出版信息

Mol Biotechnol. 1996 Feb;5(1):33-8. doi: 10.1007/BF02762410.

DOI:10.1007/BF02762410
PMID:8853014
Abstract

The Semliki Forest virus (SFV) expression vector consists of a plasmid based on the SFV infectious clone. Foreign genes may be inserted into the structural coding region, transcribed as RNA, and expressed in cell culture after transfection. RNA containing inserted sequences may be packaged into virions using a helper systems. This allows efficient infection and expression without chemical transfection, but only one round of multiplication is possible. The biosafety of the system has been increased by the introduction of multiple mutations, specifying a maturation defect, into the helper. Potential vaccines can be constructed by insertion of genes coding for antigenic proteins into the vector. Following insertion of the influenza virus nucleoprotein (NP) into the SFV vector, immunity was induced following injection of packaged or naked RNA into mice. The SFV vector is a "suicide" expression vector that has great potential for the construction of vaccines for both human and veterinary use.

摘要

Semliki森林病毒(SFV)表达载体由基于SFV感染性克隆的质粒组成。外源基因可插入结构编码区,转录为RNA,并在转染后在细胞培养物中表达。含有插入序列的RNA可使用辅助系统包装成病毒粒子。这允许在不进行化学转染的情况下进行高效感染和表达,但仅可能进行一轮增殖。通过在辅助病毒中引入多个导致成熟缺陷的突变,提高了该系统的生物安全性。通过将编码抗原蛋白的基因插入载体中,可以构建潜在的疫苗。将流感病毒核蛋白(NP)插入SFV载体后,将包装好的或裸露的RNA注射到小鼠体内可诱导免疫反应。SFV载体是一种“自杀”表达载体,在构建人用和兽用疫苗方面具有巨大潜力。

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本文引用的文献

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Expression of HIV-1 envelope glycoproteins by Semliki Forest virus vectors.塞姆利基森林病毒载体对HIV-1包膜糖蛋白的表达
AIDS Res Hum Retroviruses. 1993 Oct;9(10):963-70. doi: 10.1089/aid.1993.9.963.
2
Multiple repeating motifs are found in the 3'-terminal non-translated region of Semliki Forest virus A7 variant genome.
J Gen Virol. 1994 Jun;75 ( Pt 6):1499-504. doi: 10.1099/0022-1317-75-6-1499.
3
A single amino acid change in the E2 spike protein of a virulent strain of Semliki Forest virus attenuates pathogenicity.塞姆利基森林病毒强毒株的E2刺突蛋白中的单个氨基酸变化会减弱致病性。
Vaccine. 2007 Mar 30;25(14):2567-74. doi: 10.1016/j.vaccine.2006.07.035. Epub 2006 Aug 1.
4
Immunogene therapy of recurrent glioblastoma multiforme with a liposomally encapsulated replication-incompetent Semliki forest virus vector carrying the human interleukin-12 gene--a phase I/II clinical protocol.使用携带人白细胞介素-12基因的脂质体包裹的复制缺陷型塞姆利基森林病毒载体对复发性多形性胶质母细胞瘤进行免疫基因治疗——一项I/II期临床方案。
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Viral vectors for veterinary vaccines.兽用疫苗的病毒载体
Adv Vet Med. 1999;41:145-61. doi: 10.1016/s0065-3519(99)80014-7.
J Gen Virol. 1994 Mar;75 ( Pt 3):663-8. doi: 10.1099/0022-1317-75-3-663.
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Analysis of the molecular basis of neuropathogenesis of RNA viruses in experimental animals: relevance for human disease?实验动物中RNA病毒神经发病机制的分子基础分析:与人类疾病的相关性?
Neuropathol Appl Neurobiol. 1994 Apr;20(2):91-102. doi: 10.1111/j.1365-2990.1994.tb01167.x.
5
The alphaviruses: gene expression, replication, and evolution.甲病毒属:基因表达、复制与进化
Microbiol Rev. 1994 Sep;58(3):491-562. doi: 10.1128/mr.58.3.491-562.1994.
6
Self-replicating Semliki Forest virus RNA as recombinant vaccine.作为重组疫苗的自我复制塞姆利基森林病毒RNA
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Biotechnology (N Y). 1994 Nov;12(11):1127-31. doi: 10.1038/nbt1194-1127.
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Alphavirus expression systems.甲病毒表达系统。
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9
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Biotechnology (N Y). 1993 Aug;11(8):916-20. doi: 10.1038/nbt0893-916.