CRITICAL ROLE OF HHV8 ENCODED IRF IN AIDS LYMPHOMAS

描述：两种主要的艾滋病相关恶性肿瘤是卡波西肉瘤（KS） 和非霍奇金淋巴瘤（NHL）。 几乎所有检查的KS病变都含有 一种新的γ疱疹病毒HHV-8/KSHV，也是在一种 艾滋病免疫母细胞淋巴瘤，胸腔积液淋巴瘤（PEL）。 它 认为HHV-8在这些疾病的致病性中起作用。 HHV-8是一种B细胞嗜性病毒，编码许多非结构性蛋白。 编码细胞调节和信号蛋白同源物的基因。 它 还编码四个开放阅读框（ORF），其与 IRF家族的细胞蛋白。 IRF蛋白家族代表了一种 一组DNA结合蛋白，调节对病毒感染的反应，如 并在多种细胞反应中发挥关键作用， 淋巴细胞的凋亡、稳态、成熟和肿瘤功能 抑制基因 含有IRF-1的5q31.3染色体缺失通常是 发现于白血病。 调查人员一直对以下因素的作用感兴趣： IRF因子在病毒介导的IFN转录调控中的作用及 干扰素诱导的基因，最近，确定了这个家庭的新成员 （IRF-3），其调节细胞的生长调节和抗病毒应答。 IRF家庭的其他成员。 观察到一种已知的致病性 人疱疹病毒HHV-8编码四个ORF，与 IRF家族促使他们研究vIRF在肿瘤发生中的作用。 具体而言，他们计划：（AIM#1）表征vIRF蛋白;（AIM#2） 以确定它是否可以调节宿主对病毒的反应， IFN/干扰素诱导的信号传导;（AIM#3）以分析IFN/干扰素诱导的信号传导的潜在作用。 vIRF在细胞生长和凋亡中的作用;最后，（AIM#4）在体内评估 vIRF表达对淋巴肿瘤发生的影响 vIRF在小鼠B细胞中的表达。 因此，这些研究的结果 应该允许他们比较vIRF蛋白的性质与 细胞IRFs以及评估其体内致瘤潜力 在B细胞谱系中。 最后，vIRF转基因小鼠可能代表 一种用于未来艾滋病相关治疗研究的实验模型 淋巴瘤

DESCRIPTION: Two major AIDS-associated malignancies are Kaposi sarcoma (KS) and Non-Hodgkin's lymphoma (NHL). Nearly all KS lesions examined contained a novel type of gamma herpes virus HHV-8/KSHV which was also found in a subset of AIDSimmunoblastic lymphomas, pleural effusion lymphomas (PEL). It is assumed that HHV-8 plays a role in the pathogenicity of these diseases. The HHV-8 is a B-cell tropic virus that encodes a number of nonstructural genes encoding homologues of cell regulatory and signaling proteins. It also encodes four open reading frames (ORF) that are homologous to the cellular proteins of the IRF family. The family of IRF proteins represent a group of DNA binding proteins that modulate response to viral infection as well as play a critical role in diverse cellular responses such as apoptosis, homeostasis,maturation of lymphoid cells and function as tumor suppressor genes. The 5q31.3chromosomal deletion containing IRF-1 is often found in leukemia. The investigators have been interested in the role of IRF factors in the virus-mediated transcriptional regulation of IFN and IFN-induced genes and recently, identified a new member of this family (IRF-3) that modulates the growth regulatory and antiviral responses of the other members of the IRF family. The observation that a known pathogenic human herpesvirus, HHV-8, encodes four ORFs homologous to the proteins of the IRF family prompted them to examine the role of vIRF in oncogenesis. Specifically, they plan: (AIM#1) to characterize the vIRF protein; (AIM#2) to determine whether it can modulate host responses to virus- and IFN/cytokine-induced signaling; (AIM#3) to analyze the potential role of vIRF in cell growth and apoptosis; and finally, (AIM#4) to assess in vivo the impacts of vIRF expression to lymphoid tumorigenesis by targeting the expression of vIRF into B-cells in mice. Thus, the results of these studies should allow them to compare the properties of vIRF protein(s) with the cellular IRFs as well as to evaluate its tumorigenic potential in vivo within the B-cell lineage. Lastly, the vIRF transgenic mice may represent an experimental model for future therapeutical studies of AIDS-associated lymphomas.