Chimeric lyssavirus glycoproteins with increased immunological potential
Chimeric lyssavirus glycoproteins with increased immunological potential
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DOI：
10.1128/jvi.73.1.225-233.1999
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发表时间：
1999-01-01
影响因子：
5.4
通讯作者：
Perrin, P
中科院分区：
文献类型：
--
作者：
Jallet, C;Jacob, Y;Perrin, P
狂犬病病毒糖蛋白分子 (G) 可分为由柔性铰链分隔的两部分：NH 半部（位点 II 部分），包含抗原位点 II 直至线性区域（包含表位 VI [aa 264] 的氨基酸 [aa] 253 至 275），以及 COOH 半部（位点 III 部分），包含抗原位点 III 和跨膜区 细胞质结构域。通过细胞转染和基于小鼠 DNA 的免疫来研究每个部分的结构和免疫学作用，使用同质和嵌合 G 基因，该基因是一种基因型 (GT) 的位点 II 部分与相同或另一种 CT 的位点 III 部分融合而形成的。测试了 PV（巴斯德病毒株）狂犬病 (CTI)、Mokola (GT3) 和 EBL1（欧洲蝙蝠狂犬病病毒 1 [GT5]）病毒 G 基因之间的各种位点 II-位点 III 组合。质粒pGPV-PV、pGMok-Mok、pGMok-PV和pGEBL1-PV在神经母细胞瘤细胞中诱导正确转运和折叠的抗原的瞬时表达，并在小鼠中诱导针对亲本病毒的病毒中和抗体的表达，而pG-PVIII（仅位点III部分）和pGPV-Mok则不然。 PV (GT1) 的位点 III 部分是 T 辅助细胞的强诱导剂，并且在呈现各种 GT 的位点 II 部分方面非常有效。这两个部分都是嵌合 G 蛋白正确折叠和运输所必需的，这对于免疫学研究和多价疫苗的开发具有强大的潜在价值。嵌合质粒 pGEBL1-PV 拓宽了针对欧洲狂犬病病毒基因型（GT1、GT5 和 GT6）的保护谱。
The rabies virus glycoprotein molecule (G) can be divided into two parts separated by a flexible hinge: the NH, half (site II part) containing antigenic site II up to the linear region (amino acids [aa] 253 to 275 encompassing epitope VI [aa 264]) and the COOH half (site III part) containing antigenic site III and the transmembrane and cytoplasmic domains. The structural and immunological roles of each part were investigated by cell transfection and mouse DNA-based immunization with homogeneous and chimeric G genes formed by fusion of the site II part of one genotype (GT) with the site III part of the same or another CT. Various site II-site III combinations between G genes of PV (Pasteur virus strain) rabies (CTI), Mokola (GT3), and EBL1 (European bat lyssavirus 1 [GT5]) viruses were tested. Plasmids pGPV-PV, pGMok-Mok, pGMok-PV, and pGEBL1-PV induced transient expression of correctly transported and folded antigens in neuroblastoma cells and virus-neutralizing antibodies against parental viruses in mice, whereas, pG-PVIII (site III part only) and pGPV-Mok did not. The site III part of PV (GT1) was a strong inducer of T helper cells and was very effective at presenting the site II part of various GTs. Both parts are required for correct folding and transport of chimeric G proteins which have a strong potential value for immunological studies and development of multivalent vaccines. Chimeric plasmid pGEBL1-PV broadens the spectrum of protection against European lyssavirus genotypes (GT1, GT5, and GT6).