ONCOGENIC POTENTIAL OF HIV

超过20%的HIV-1感染者最终会发展为 B细胞淋巴瘤。从历史上看，这一事件被归因于 免疫功能障碍和不能直接感染和转化的B- 通过艾滋病病毒传播的细胞。然而，通过使用有限稀释PCR， (聚合酶链式反应)，一种相对较新的技术 应用于艾滋病淋巴瘤，我们已经获得了高负荷的证据 艾滋病相关B细胞淋巴瘤亚群中的艾滋病毒前病毒(3/14)。 这3例肿瘤均为非易位病例。此外，我们还有 获得的证据表明这些肿瘤是多克隆的，这增加了 转化可能由HIV特异性介导的可能性 蛋白。此外，我们最近发现艾滋病毒可以感染和 体外恶性转化B细胞群(1，2)，前提是 目标人群中至少有一些细胞含有EBV。我们的转型 B-HIV株，每个细胞含有一个HIV前病毒和一个EBV基因组，生长 在1%血清中，在软琼脂中克隆，并在SCID中形成恶性肿瘤 老鼠。这些结果导致了一种假设，即艾滋病毒感染B- 细胞可能与EBV共同作用，可能是艾滋病的一个亚组的直接原因- 相关的淋巴瘤。因为这个假设很重要，也很新颖 由于存在争议，这项提案的4个目标范围从更彻底的 B细胞肿瘤材料的分析，以原位应用 杂交法同时检测HIV和EBV 序列，通过直接测试HIV基因产品的能力 与EB病毒一起导致B-细胞恶性转化 细胞。我们的具体目标是：a.分析额外的艾滋病B细胞 淋巴瘤。B细胞淋巴瘤克隆性的测定 含有大量的艾滋病毒前病毒。C.艾滋病病毒和EB病毒的检测 转化细胞和肿瘤细胞进行原位杂交。D.使用 B细胞转化试验确定S参与的基因 EB病毒感染的B细胞群体中的恶性转化。与艾滋病相关的 淋巴瘤是艾滋病毒感染者死亡的主要原因。 我们的实验是新颖的，有可能提供证据 HIV可以在体内转化B细胞产生 淋巴瘤。

Greater than twenty percent of HIV-1 infected will eventually develop a B-cell lymphoma. Historically, this incidence has been attributed to immune dysfunction and not to direct infection and transformation of B- cells by HIV. However, through the use of limiting dilution PCR (Polymerase Chain Reaction), a relatively new technique not previously applied to AIDS lymphomas, we have obtained evidence of a high load of HIV provirus in a subset (3 of 14) of AIDS-related B-cell lymphomas. These 3 tumors are all non-translocation cases. In addition, we have obtained evidence that these tumors are polyclonal which raises the possibility that transformation may be mediated by an HIV-specific protein. Furthermore, we have recently found that HIV can infect and malignantly transform B-cells populations in vitro (1,2), provided that at least some cells in the target population contain EBV. Our transformed line, B-HIV, contains one HIV provirus per cell and one EBV genome, grows in 1% serum, clones in soft agar, and forms malignant tumors in SCID mice. These results have led to the hypothesis that HIV infection of B- cells may in concert with EBV, can be a direct cause of a subset of AIDS- related lymphomas. Because this hypothesis is important and novel as well as controversial, the 4 aims of this proposal range from a more thorough analysis of B-cell tumor material, to the application of in situ hybridization for testing for the parallel presence of both HIV and EBV sequences, through to direct testing of the ability of HIV gene products to cause, in conjunction with EBV, the malignant transformation of B- cells. Our specific aims are: a. Analysis of additional AIDS B-cell lymphomas. b. Determination of the clonality of B-cell lymphomas containing a high load of HIV provirus. c. Detection of HIV and EBV in transformed cells and tumor cells by in situ hybridization. d. Use of a B-cell transformation assay to determine the gene(s) involved in malignant conversion in EBV infected B-cell populations. AIDS-related lymphomas represent a major cause of death for HIV-infected individuals. Our experiments are novel and have the potential of providing evidence of a mechanism by which HIV could transform B-cells in vivo generating lymphoma.