Replication-competent rhabdoviruses with human immunodeficiency virus type 1 coats and green fluorescent protein: Entry by a pH-independent pathway
Replication-competent rhabdoviruses with human immunodeficiency virus type 1 coats and green fluorescent protein: Entry by a pH-independent pathway
复制标题
DOI：
10.1128/jvi.73.8.6937-6945.1999
复制
发表时间：
1999-08-01
影响因子：
5.4
通讯作者：
Rose, JK
中科院分区：
文献类型：
--
作者：
Boritz, E;Gerlach, J;Rose, JK
我们描述了一种具有复制能力的重组水泡性口炎病毒（VSV），其中编码单跨膜糖蛋白（G）的基因被删除，并被编码与VSV G胞质结构域融合的人类免疫缺陷病毒1型（HIV-1）包膜蛋白的胞外和跨膜结构域的env-G杂合基因所取代。添加编码绿色荧光蛋白的额外基因以允许快速检测感染。这种新的替代病毒在表达HIV受体CD 4和辅助受体CXCR 4的细胞上感染和繁殖。感染被CXCR 4的配体SDF-1、CD 4抗体和HN中和抗体阻断。与VSV不同，这种病毒通过pH非依赖性途径进入细胞，因此支持HIV进入的pa非依赖性途径。携带来自R5或X4 R5 HIV毒株的杂合env-G基因的其他重组体也显示出它们所来源的HIV毒株的辅助受体特异性。这些替代病毒为HIV中和抗体提供了一种简单而快速的检测方法，并快速筛选干扰HIV结合或进入任何阶段的分子。这些病毒也可能用作HIV疫苗。我们的研究结果表明，广泛的应用其他替代病毒的基础上VSV。
We describe a replication-competent, recombinant vesicular stomatitis virus (VSV) in which the gene encoding the single transmembrane glycoprotein (G) was deleted and replaced by an env-G hybrid gene encoding the extracellular and transmembrane domains of a human immunodeficiency virus type 1 (HIV-1) envelope protein fused to the cytoplasmic domain of VSV G. An additional gene encoding a green fluorescent protein was added to permit rapid detection of infection. This novel surrogate virus infected and propagated on cells expressing the HIV receptor CD4 and coreceptor CXCR4. Infection was blocked by SDF-1, the ligand for CXCR4, by antibody to CD4 and by HN-neutralizing antibody. This virus, unlike VSV, entered cells by a pH-independent pathway and thus supports a pa-independent pathway of HIV entry. Additional recombinants carrying hybrid env-G genes derived from R5 or X4R5 HIV strains also showed the coreceptor specificities of the HIV strains from which they were derived. These surrogate viruses provide a simple and rapid assay for HIV-neutralizing antibodies as well as a rapid screen for molecules that would interfere with any stage of HIV binding or entry. The viruses might also be useful as HIV vaccines. Our results suggest wide applications of other surrogate viruses based on VSV.