GENETIC INTERACTION OF HUMAN HERPESVIRUS-6 WITH HIV-1

进行分子研究来识别和表征人类 可激活人类免疫缺陷的疱疹病毒 6 (HHV-6) 基因 病毒（HIV）启动子。 疱疹病毒家族的成员经常与获得性感染有关 免疫缺陷综合症（艾滋病）。 HHV-6 最初是从 艾滋病患者和淋巴组织增生性疾病患者。 HHV-6 可有效感染许多与 HIV-1 相同的细胞类型， 尤其是 CD4 T 细胞，几乎每个人都携带 HHV-6。 共同 HIV-1 和 HHV-6 感染 T 细胞会导致细胞病变增加 影响。 据推测，HHV-6 在加速该过程中发挥辅助因子作用。 艾滋病的发展。 HHV-6 可以激活 T 细胞系中的 HIV-1 启动子。 通过引入DNA 进入培养的细胞中，我们已经证明了 HHV-6 基因片段，它可以 引起小鼠细胞和人类角质形成细胞的致瘤性转化，ca 增加指示剂氯霉素乙酰转移酶的表达 (CAT) 基因与 HIV-1 启动子相连。 这种激活是介导的 通过 HIV-1 启动子中存在的 Sp1（细胞因子）结合位点 旨在阻断 Sp1 结合位点。 为了有效激活，需要多个 Sp1 位点 需要。 HIV-1 启动子的 NF-kB 位点对于 HHV-6 不是必需的 基因介导的激活。 我们对缺失克隆的初步研究 在 HHV-6 中鉴定出一个小蛋白质（115 个氨基酸）编码序列 参与该功能的基因片段。 需要进一步研究 证实该蛋白在 HIV-1 启动子激活中的作用。 这项研究对于了解 HHV-6 如何在 HIV 中发挥作用非常重要 发病机制。 该项目还将提供知识和工具 开发新型抗病毒疗法和安全的基因病毒载体 艾滋病的治疗。

Molecular studies were performed to identify and characterize the human herpesvirus-6 (HHV-6) genes that can activate the Human immunodeficiency virus (HIV) promoter. Members of the herpesvirus family are frequently associated with acquired immunodeficiency syndrome (AIDS). HHV-6 was initially isolated from patients with AIDS and form patients with lymphoproliferative disorders. HHV-6 productively infects many of the same cell types as HIV-1, particularly CD4 T cells and nearly every individual carries HHV-6. Co- infection of T cells with HIV-1 and HHV-6 leads to increased cytopathic effects. It is postulated that HHV-6 plays a cofactor role in hastening th development of AIDS. HHV-6 can activate the HIV-1 promoter in T-cell lines. By introducing DNA into cells in culture, we have shown that a HHV-6 gene segment, which can cause tumorigenic transformation of mouse cells and human keratinocytes, ca increase the expression of the indicator chloramphenicol acetyltransferase (CAT) gene linked to the HIV-1 promoter. This activation was mediated through a Sp1 (cellular factor) binding site present in the HIV-1 promoter and activation was dramatically reduced by oligomers designed to block the Sp1 binding sites. For efficient activation, more than one Sp1 site were required. NF-kB sites of the HIV-1 promoter were not essential for HHV-6 gene mediated activation. Our initial studies with deletion clones identified a small protein (115 amino acids) coding sequence in the HHV-6 gene segment involved in this function. Further studies are necessary to confirm the role of this protein in the activation of the HIV-1 promoter. This study is important to understand how HHV-6 could play a role in HIV pathogenesis. The project will also provide knowledge and tools for development of novel antiviral therapies and safe viral vectors for gene therapy of AIDS.