Characterization of vesicular stomatitis virus recombinants that express and incorporate high levels of hepatitis C virus glycoproteins

Characterization of vesicular stomatitis virus recombinants that express and incorporate high levels of hepatitis C virus glycoproteins
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DOI:
10.1128/jvi.76.14.6865-6872.2002
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发表时间:
2002-07-01
影响因子:
5.4
通讯作者:
Rose, JK
Rose, JK
中科院分区:
医学2区
文献类型:
--
作者:
Buonocore, L;Blight, KJ;Rose, JK

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我们产生了重组水泡性口炎病毒(VSV)表达的基因编码的杂合蛋白的丙型肝炎病毒(HCV)糖蛋白的胞外结构域融合在不同的位置的VSV G糖蛋白(E1G和E2G)的跨膜和胞质结构域。我们表明,这些嵌合蛋白被运送到细胞表面,并纳入VSV病毒粒子有效。我们还产生了VSV重组体,其中编码VSV G蛋白的基因被缺失并被E1 G和E2 G基因中的一个或两个以及绿色荧光蛋白基因取代。这些AG病毒掺入的E1G和E2G蛋白的水平大约相当于VSV G本身的正常水平,或每个病毒粒子约1,200个每种蛋白分子。考虑到VSV重组体在其他研究中作为疫苗的效力,HCV蛋白的这种高水平表达和掺入病毒体中对于HCV疫苗的开发可能是非常重要的。尽管病毒体中存在高水平的E1G和E2G蛋白,但这些病毒体不感染已报道支持至少低水平HCV感染和复制的细胞系。
We generated recombinant vesicular stomatitis viruses (VSV) expressing genes encoding hybrid proteins consisting of the extracellular domains of hepatitis C virus (HCV) glycoproteins fused at different positions to the transmembrane and cytoplasmic domains of the VSV G glycoprotein (E1G and E2G). We show that these chimeric proteins are transported to the cell surface and incorporated into VSV virions efficiently. We also generated VSV recombinants in which the gene encoding the VSV G protein was deleted and replaced by one or both of the E1G and E2G genes, together with a green fluorescent protein gene. These AG viruses incorporated E1G and E2G proteins at levels approximately equivalent to the normal level of VSV G itself, or about 1,200 molecules of each protein per virion. Given the potency of VSV recombinants as vaccines in other studies, this high-level expression and incorporation of HCV proteins into virions could be very important for development of an HCV vaccine. Despite the presence of E1G and E2G proteins at high levels in the virions, these virions did not infect cell lines that have been reported to support at least a low level of HCV infection and replication.