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Matrix蛋白和G蛋白双位点突变型水泡性口炎病毒的构建及生物学活性观察 被引量:3

Construction and Characterization of Recombinant VSV with Double Mutation in M and G Protein
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摘要 重组水泡性口炎病毒(Vesiclar stomatitis virs,VSV)是一种具有良好应用前景的病毒载体,可应用于制备疫苗和治疗肿瘤,但该载体仍存在安全性问题,高剂量注射实验动物可导致产生神经毒性。为减低乃至去除野生型VSV的致病性,作者针对VSV毒力因子,构建了Matrix蛋白和G蛋白双位点突变型重组VSV,该病毒敲除了原来Matrix蛋白的第51位精氨酸和G蛋白C末端的28个氨基酸。相比野生型VSV,新病毒的致病性显著降低。试验也证实这个致弱的病毒是由于2种不同弱化机理共同作用所致,即I型干扰素作用和复制能力减低。新型VSV病毒载体有希望成为一个更安全、有效的疫苗载体。 Recombinant Vesiclar stomatitis virs(VSV) is an ideal viral vector for vaccine and virotherapy,however,there still exists toxicities in VSV vector.Animals exhibited neurotoxicity when injected with high dose of VSV.In order to decrease the pathogenesis by wild-typed VSV,recombinant VSV aiming at its virulent factors was developed,which included deletion of methionine 51 in matrix protein and truncation of 28 amino acids at carboxyl terminal of G protein.In comparison with wild-typed VSV,VSV△M51-G△28-GFP indicated significant attenuation not only in vitro but in vivo as well.The attenuation was proved based on two different mechanisms,including type I interferon inhibition and viral replication shortage.This novel VSV can be a promising vector for both vaccine and tumor treatment.
出处 《畜牧兽医学报》 CAS CSCD 北大核心 2011年第6期823-829,共7页 ACTA VETERINARIA ET ZOOTECHNICA SINICA
基金 农业部南方都市农业重点实验室开放课题 上海市兽医生物技术重点实验室开放课题
关键词 水泡性口炎病毒 病毒载体 致病性 vesicular stomatitis virus viral vector pathogenesis
作者简介 作者简介:方心葵(1970-),女,河南人,博士,副教授,主要从事生物化学与分子生物学研究,Tel:021-34207240,E-mail:xinkuifang@sjtu.edu.cn 通讯作者:孙涛,Tel:02134207240,E-mail:tao.sun@sjtu.edu.cn
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参考文献13

  • 1SCHNELL M J, BUONOCORE L, KRETZSCHMAR E,et al. Foreign glycoproteins expressed from recom- binant vesicular stomatitis viruses are incorporated ef- ficiently into virus particles[J]. Proc Natl Acad Sci U S A,1996 ,93(21):11359-11365.
  • 2MAJID A M, EZELLE H, SHAH S, et al. Evaluating replication-defective vesicular stomatitis virus as a vaccine vehicle[J]. J Virol,2006 ,80(14):6993- 7008.
  • 3GARBUTT M, LIEBSCHER R,WAHL-JENSEN V, et al. Properties of replication-competent vesicular stomatitis virus vectors expressing glycoproteins of filoviruses and arenaviruses[J]. J Virol, 2004, 78 (10) :5458-5465.
  • 4温志远,葛金英,王永,胡森,郝永清,步志高.水泡性口炎病毒印第安纳株反基因操作系统的建立[J].中国预防兽医学报,2006,28(5):489-494. 被引量:10
  • 5邓宏魁,丁明孝,聂玉春,等.重组VSV病毒载体和重组VSV病毒及其制备方法和用途[P].中国专利申请号:03156144.6.4.
  • 6JOHNSON J E, NASAR F, COLEMAN J W, et al. Neurovirulence 4properties of recombinant vesicular stomatitis virus vectors in non-human primates[J]. Virol,2007,360(1) :36-49.
  • 7BI Z,BARNA M,KOMATSU T, et al. Vesicular sto- matitis virus infection of the central nervous system activates both innate and acquired immunity[J]. J Virol,1995,69(10) :6466-6472.
  • 8STOJDL DF, LICHTY BD, TENOEVER BR, et al. VSV strains with defects in their ability to shutdown innate immunity are potent systemic anti-cancer agents[J]. Cancer Cell, 2003,4(4) : 263-275.
  • 9OWENS R J, ROSE J K. Cytoplasmic domain re- quirement for incorporation of a foreign envelope pro- tein into vesicular stomatitis virus[J]. J Virol, 1993, 67(1) :360-365.
  • 10DIAZ M O,ZIEMIN S,LE BEAU M M,et al. Ho- mozygous deletion of the alpha- and beta 1-interferon genes in human leukemia and derived cell lines[J]. Proc Natl Acad Sci US A,1988,85(14):5259-5263.

二级参考文献20

  • 1Barr J N. Transcriptional control of the RNA-dependent RNA polymerase of vesicular stomatitis virus [J]. Biochim Biophys Acta, 1577: 337-353.
  • 2Lawson N D , Stillman E A, Whitt M A, et al. Recombinant vesicular stomatitis viruses from DNA [J]. Proc Nat I Acad Sci, 1995, 92: 4477-4481.
  • 3Whelan S J, Ball L A, Barr J N, et al. Efficient recovery of infectious vesicular stomatitis virus entirely from cDNA clones[J].Proc Nat I Acad Sci, 1995, 92: 8388-8392.
  • 4Roberts A, Kretzschmar E, Kawaoka Y , et al.Vaccination with a recombinant vesicular stomatitis virus expressing an influenza virus hemagglutinin provides complete protection from influenza virus challenge [J]. J Virol, 1998, 72(6): 4704-4711.
  • 5Rose N F. An effect ive AIDS vaccine base d on live attenuated vesicular stomatitis virus recombinants [J ]. Cell, 2001, 106: 539- 549.
  • 6Stojdl D F. VSV strains with defects in their ability to shutdownin nate immunity are potent systemic anti-cancer agents[J]. Cancer Cell, 2003, 4: 263-275.
  • 7Schurer H, Lang K, Schuster J, et al. A universal method to produce in vitro transcripts with homogeneous 3' ends[J].Nucleic Acid Research, 2002, 30: (12) 56.
  • 8Takada A C, Robison H, Goto A, et al. A system for functional analysis of Ebola virus glycoprotein [J]. Proc Natl Acad Sci,1997, 94: 14764-14769.
  • 9Inoue K, Shoji Y, Kurane I, et al. An improved method for recovering rabies virus from cloned cDNA[J]. J Med Virol, 2002,107: 229-236.
  • 10Stillman E A, J K Rose, M A Whitt. Replication and Amplification of Novel Vesicular Stomatitis Virus Minigenomes Encoding Viral Structural Proteins[J]. J Virol, 1995, 69: 2946-2953.

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