HIV CHEMOKINE-LIKE PROTEINS

人类免疫缺陷病毒（HIV-1）进入细胞需要病毒包膜蛋白（gp-120/gp 41）和细胞受体、CD 4和趋化因子受体。然而，谜团依然存在。一些HIV病毒株可以感染表面缺乏CD 4的细胞。尽管最近解决了与双结构域CD 4和Fab片段（I7 b）复合的截短gp- 120的晶体结构，但尚不清楚复合物如何与细胞趋化因子受体相互作用，也不清楚这种相互作用是否直接。我们已经确定了一个HIV-1反义基因，它除了产生反义转录物外，还可能编码一组趋化因子样蛋白。将该基因导入稳定表达包膜蛋白趋化因子受体（CXCR 4）的几种细胞系中可诱导细胞死亡和合胞体形成。这表明HIV-1反义基因可能通过提供参与与细胞趋化因子受体相互作用的趋化因子基序，在导致细胞融合和单细胞裂解的事件中发挥作用。我们推测，这种病毒编码的反义基因编码的HIV趋化因子样蛋白有助于病毒入侵介导结合细胞趋化因子受体，也许与gp-120。我们计划用单细胞溶解的生物测定法来研究这一点.此外，我们将进一步鉴定和分离HIV趋化因子样蛋白，并研究有助于反义启动子活性的HW-1基因元件。

The human immunodeficiency virus (HIV-1) entry into cells requires tile viral envelope proteins (gp-120/gp4l) and cellular receptors, CD4 and chemokine receptors. Yet puzzles remain. Some strains of HIV can infect cells lacking CD4 on their surface. Despite the recent solving of the crystal structure of a truncated gp- 120 complexed to two-domain CD4 and an Fab fragment (I7b), it is not clear how the complex interacts with the cellular chemokine receptor, nor if this interaction is direct. We've identified an HIV-I antisense gene, that in addition to producing antisense transcripts, could potentially encode a set of chemokine-like proteins. Introduction of this gene into several cell lines that stably express envelope proteins chemokine receptors (CXCR 4) induces cell death and syncytium formation. This indicates that the HIV-1 antisense gene plays a role in events leading to cell fusion and single-cell lysis, perhaps by providing the chemokine motif that participates in interaction with cellular chemokine receptors. We postulate that this virally encoded antisense gene coding for HIV chemokine-like proteins contributes to viral invasion by mediating binding to the cellular chemokine receptor, perhaps in conjunction with gp-120. We plan to investigate this using a bioassay investigating single- cell lysis. In addition, we will further characterize and isolate the HIV chemokine-like protein(s), and investigate the HW-I gene elements contributing to the antisense promoter activity.