ATTENUATION OF VENEZUELAN EQUINE ENCEPHALITIS-VIRUS STRAIN TC-83 IS ENCODED BY THE 5'-NONCODING REGION AND THE E2 ENVELOPE GLYCOPROTEIN
ATTENUATION OF VENEZUELAN EQUINE ENCEPHALITIS-VIRUS STRAIN TC-83 IS ENCODED BY THE 5'-NONCODING REGION AND THE E2 ENVELOPE GLYCOPROTEIN
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DOI：
10.1128/jvi.67.3.1269-1277.1993
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发表时间：
1993-03-01
影响因子：
5.4
通讯作者：
TRENT, DW
中科院分区：
文献类型：
--
作者：
KINNEY, RM;CHANG, GJ;TRENT, DW
委内瑞拉马脑炎(VEE)病毒特立尼达驴(TRD)毒株及其减毒活疫苗衍生毒株TC-83病毒具有不同的神经毒力特征。在噬菌体T7启动子后面构建了TC-83病毒基因组的全长cDNA克隆。为了确定TC-83病毒减毒的基因组决定因素，通过体外诱变或重组将TRD病毒特异性序列插入到TC-83病毒克隆中。用VEE E2和E1特异性单抗对重组病毒进行抗原性分析，可预测其抗原性。小鼠攻击实验表明，导致TC-83病毒减毒表型的遗传标记由基因组5‘非编码区第3位核苷酸和E2包膜糖蛋白组成。TC-83病毒的E2-120位氨基酸似乎是病毒衰减率的主要结构决定因素。将TRD病毒特异的5‘非编码区插入到TC-83病毒全长克隆中并不能改变病毒的减毒表型。然而，TRD病毒特异的5‘非编码区增强了TRD病毒下游氨基酸序列的毒力。
The virulent Trinidad donkey (TRD) strain of Venezuelan equine encephalitis (VEE) virus and its live attenuated vaccine derivative, TC-83 virus, have different neurovirulence characteristics. A full-length cDNA clone of the TC-83 virus genome was constructed behind the bacteriophage T7 promoter in the polylinker of plasmid pUC18. To identify the genomic determinants of TC-83 virus attenuation, TRD virus-specific sequences were inserted into the TC-83 virus clone by in vitro mutagenesis or recombination. Antigenic analysis of recombinant viruses with VEE E2- and E1-specific monoclonal antibodies gave predicted antigenic reactivities. Mouse challenge experiments indicated that genetic markers responsible for the attenuated phenotype of TC-83 virus are composed of genome nucleotide position 3 in the 5'-noncoding region and the E2 envelope glycoprotein. TC-83 virus amino acid position E2-120 appeared to be the major structural determinant of attenuation. Insertion of the TRD virus-specific 5'-noncoding region, by itself, into the TC-83 virus full-length clone did not alter the attenuated phenotype Of the virus. However, the TRD virus-specific 5'-noncoding region enhanced the virulence potential of downstream TRD virus amino acid sequences.