Increased immunogenicity and protective efficacy in outbred and inbred mice by strategic carboxyl-terminal truncation of Japanese encephalitis virus envelope glycoprotein.
Increased immunogenicity and protective efficacy in outbred and inbred mice by strategic carboxyl-terminal truncation of Japanese encephalitis virus envelope glycoprotein.
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通过策略性地截断日本脑炎病毒包膜糖蛋白的羧基末端，提高远交和近交小鼠的免疫原性和保护功效。
DOI：
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发表时间：
1993
影响因子：
3.3
通讯作者：
Hideo Sumiyoshi
中科院分区：
文献类型：
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作者：
L. Jan;L. S. Henchal;Czau;Peter L. Summers;Ching;Doria Dubois;Hideo Sumiyoshi
我们构建了表达日本脑炎病毒（JEV）全长包膜(E)糖蛋白或战略性截断的E糖蛋白约80% n端序列的重组痘苗病毒，并比较了它们在小鼠体内的抗原结构和保护性免疫。乙脑病毒E糖蛋白序列的截断位点对应于已被证明增加登革热4型或2型病毒E糖蛋白免疫原性的位置。重组病毒感染细胞中JEV E糖蛋白的分析表明，c端截短的E保留了与全长E糖蛋白相似的抗原结构。全长乙脑糖蛋白主要在细胞内检测到，而在细胞表面检测到一小部分（< 2%）。另一方面，截断的80% E糖蛋白在细胞内运输途径中表现出改变，导致细胞表面的积累增加（10-25%），分泌增加（6-10%）到培养基中。与全长E糖蛋白相比，c端截短的E糖蛋白在远交系CD-1小鼠以及两种对腹腔乙脑病毒感染具有不同抵抗力的近交系小鼠中诱导了更大的抗体反应和更高水平的保护性免疫。在远交系CD-1和近交系C57/Bl小鼠中，具有显性常染色体遗传位点控制对高剂量乙脑病毒感染的抗性或获得对脑内乙脑病毒感染的抗性的能力，截短的E糖蛋白诱导更高滴度的乙脑病毒中和抗体。
We constructed recombinant vaccinia viruses expressing the full-length envelope (E) glycoprotein of Japanese encephalitis virus (JEV) or a strategically truncated E glycoprotein, approximately 80% of the N-terminal sequence, and compared their antigenic structure and protective immunity in mice. The truncation site in the JEV E glycoprotein sequence corresponds to the position that had been shown to increase the immunogenicity of dengue type 4 or type 2 virus E glycoprotein. Analysis of the JEV E glycoprotein in recombinant virus-infected cells showed that C-terminally truncated E retains an antigenic structure similar to that of the full-length E glycoprotein. The full-length JEV E glycoprotein was detected predominantly intracellularly, while a small fraction (< 2%) was present on the cell surface. On the other hand, the truncated 80% E glycoprotein exhibited an alteration in the intracellular transport pathway resulting in increased accumulation (10-25%) on the cell surface and secretion (6-10%) into the medium. The C-terminally truncated E glycoprotein induced a greater antibody response and a higher level of protective immunity than did the full-length E glycoprotein in outbred CD-1 mice as well as in two strains of inbred mice that differ in their resistance to intraperitoneal (ip) JEV infection. In the case of outbred CD-1 and inbred C57/Bl mice, which possess a dominant autosomal genetic locus that controls resistance to a high dose of ip infection of JEV or the capacity to acquire resistance to intracerebral JEV infection, truncated E glycoprotein induced a higher titer of JEV neutralizing antibodies.