Role of V3 independent domains on a dualtropic human immunodeficiency virus type 1 (HIV-1) envelope gp120 in CCR5 coreceptor utilization and viral infectivity
Role of V3 independent domains on a dualtropic human immunodeficiency virus type 1 (HIV-1) envelope gp120 in CCR5 coreceptor utilization and viral infectivity
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DOI：
10.1111/j.1348-0421.2001.tb02653.x
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发表时间：
2001-01-01
影响因子：
2.6
通讯作者：
Maeda, Y
中科院分区：
文献类型：
--
作者：
Foda, M;Harada, S;Maeda, Y
人类免疫缺陷病毒1型（HIV-1）进入细胞的分子机制涉及病毒包膜糖蛋白gp120与两种靶细胞蛋白（CD4和CCR5或CXCR4趋化因子受体）之间的特异性相互作用。我们使用了一组嵌合病毒，其中来自双嗜性HIV-1（KMT）分离物的gp120的V1/V2和V3结构域被单独或联合引入到嗜t型HIV-1（NI+3）背景中。使用表达CD4和CCRS趋化因子受体的细胞系，将这些嵌合结构用于细胞-细胞融合和无细胞病毒感染性试验。在这两项试验中，HIV-1的V3结构域（KMT）而不是V1/V2结构域被证明是CCR5辅助受体使用的主要决定因素。然而，在无细胞病毒感染性实验中，尽管具有HIV-1(KMT) V1/V2和V3结构域的嵌合病毒能有效地与共受体表达细胞融合，但其在CCRS和CXCR4表达细胞中的感染性明显降低，恢复这种嵌合病毒的感染水平需要引入HIV-1（KMT）的C3-V5结构域。我们目前的研究结果证实，V3结构域是融合活性和细胞趋向性的主要决定因素，并且证明了V1/V2结构域的不可缺少的作用，此外，当相应的V1/V2和V3结构域存在时，C3-V5结构域似乎在病毒感染性中起重要作用。
The molecular mechanism of human immunodeficiency virus type 1 (HIV-1) entry into cells involves specific interactions between the viral envelope glycoprotein gp120 and two target cell proteins, CD4 and either CCR5 or CXCR4 chemokine receptors, In order to delineate the functional role of HIV-1 gp120 subdomains of dualtropic strains in CCR5 coreceptor usage, we used a panel of chimeric viruses in which the V1/V2 and V3 domains of gp120 from the dualtropic HIV-1(KMT) isolate were introduced either alone or in combination into the T-tropic HIV-1(NI+3) background. These chimeric constructs were employed in cell-cell fusion and cell-free virus infectivity assays using cell lines expressing CD4 and the CCRS chemokine receptor. In both assays, the V3 domain of HIV-1(KMT) but not the V1/V2 domain proved to be the principal determinant of CCR5 coreceptor usage. However, in the cell-free viral infectivity assay although a chimeric virus with a combined V1/V2 and V3 domains of HIV-1(KMT) efficiently fused with coreceptor expressing cells, yet its infectivity was markedly diminished in CCRS as well as CXCR4 expressing cells, Restoring a comparable level of infection of such chimeric virus required the C3-V5 domain from HIV-1(KMT) to be introduced. Our present findings confirmed that the V3 domain is the major determinant of fusion activity and cellular tropism, and demonstrated a dispensable role for the V1/V2 domain, In addition the C3-V5 domain appeared to play an important role in viral infectivity when the corresponding V1/V2 and V3 domains are present.