Mechanism of Action LANA Encoded by KSHV

描述（由申请方提供）：卡波西肉瘤疱疹病毒（KSHV）是 一种与包括卡波西氏病在内的人类恶性肿瘤相关的γ疱疹病毒 肉瘤和体腔淋巴瘤（BCBL）或胸腔积液淋巴瘤 （PELs）。潜伏相关核抗原（拉娜）是一种组成性的 在所有潜伏感染的KSHV细胞中表达，并参与 KSHV基因组的维持和转录调控。拉娜将 KSHV基因组通过与顺式作用DNA的结合而与宿主染色体结合 在病毒基因组的左边的元素。拉娜还与 包括组蛋白H1在内的染色体蛋白质潜在地束缚着病毒 基因组到宿主染色体。越来越多的证据表明 这表明拉娜对于KSHV在人类恶性肿瘤中的持续性是至关重要的。 本研究的具体目标是：（1）研究拉娜在 调节KSHV感染的病毒和细胞基因表达 生长转化的细胞。(2)识别和表征相关的拉娜 蛋白质，并确定这些蛋白质的功能后果 特定. (3)鉴定KSHV基因组上拉娜的其他结合位点 （4）确定拉娜的功能结构域，它参与DNA的合成 KSHV基因组在感染细胞中的结合、转录调控和维持 细胞这些目标将为阐明 拉娜参与KSHV发病机制的机制， 相关的人类恶性肿瘤。

DESCRIPTION (Provided by the applicant): Kaposi's sarcoma herpesvirus (KSHV) is a gammaherpesvirus associated with human malignancies including Kaposi's sarcoma and body cavity based lymphomas (BCBLs) or pleural effusion lymphomas (PELs). One of the latency-associated nuclear antigen (LANA) is constitutively expressed in all latently infected KSHV cells and is involved in the maintenance of the KSHV genome and transcriptional regulation. LANA tethers the KSHV genome to host chromosomes through association with cis-acting DNA element(s) at the left of the viral genome. LANA also associates with chromosomal proteins including histone H 1 potentially tethering the viral genome to host chromosome. There is an increasing body of evidence demonstrating that LANA is critical for KSHV persistence in human malignancies. The specific aims of this proposal are: (1) To investigate the role of LANA in regulating viral and cellular gene expression in KSHV infected growth-transformed cells. (2) To identify and characterize LANA associated proteins and to determine the functional consequences resulting for these specific. (3) To identify additional binding sites for LANA on the KSHV genome and (4) to determine functional domains of LANA which is involved in DNA binding, transcriptional regulation and maintenance of KSHV genome in infected cells. These aims will provide critical information for elucidating the mechanisms by which LANA functions in contributing to KSHV pathogenesis and associated human malignancies.