Changes in viral and cellular gene expression mediated by KSHV PAN lncRNA

项目摘要 卡波西肉瘤相关疱疹病毒或人疱疹病毒8（KSHV/HHV 8）是一种γ疱疹病毒， 是卡波西肉瘤和体腔淋巴瘤的病因在裂解再活化过程中，KSHV产生一种 高丰度核定位转录物，多聚腺苷酸化核RNA，PAN RNA。PAN RNA被证明 调节病毒和细胞基因表达。PAN RNA使用的一种机制涉及介导 表观遗传修饰的变化。PAN RNA表达缺陷的重组BACmid不能 再活化并产生上清液病毒。这确立了PAN RNA作为一种必需的长非编码RNA （lncRNA）用于病毒复制和生长。 lncRNA被定义为长度超过200个碱基的非蛋白质编码转录物。在哺乳动物细胞中，lncRNA 非常丰富，估计有数万人，其中许多人与疾病有关。 许多lncRNA现已被表征并具有广泛的功能。许多人采取行动， 通过各种机制进行转录。lncRNA可以作为转录的调节因子，通过直接 与转录因子相互作用以及将转录复合物募集到特异性启动子。为 在疱疹病毒中，现在已经鉴定了几种lncRNA，包括KSHV PAN RNA，人巨细胞病毒 9和单纯疱疹病毒（HSV-1）LAT。然而，充分认识的作用 疱疹病毒编码的lncRNA在感染中处于婴儿期。目前迫切需要界定 疱疹病毒lncRNA及其对病毒复制贡献和对细胞基因表达的影响。

PROJECT SUMMARY Kaposi's sarcoma associated herpesvirus or human herpesvirus 8 (KSHV/HHV8) is a gamma herpesvirus that is the cause of Kaposi's sarcoma and body cavity lymphomas. During lytic reactivation, KSHV produces a highly abundant nuclear localized transcript, polyadenylated nuclear RNA, PAN RNA. PAN RNA was shown to regulate viral and cellular gene expression. One mechanism used by PAN RNA involves the mediation of changes in epigenetic modifications. A recombinant BACmid defective for PAN RNA expression fails to reactivate and produce supernatant virus. This established PAN RNA as an essential long non-coding RNA (lncRNA) for virus replication and growth. lncRNAs are defined as non protein coding transcripts longer than 200 bases. In mammalian cells lncRNAs are very abundant with numbers estimated in the tens of thousands and many are associated with disease. Many lncRNAs have now been characterized and have a broad range of functions. Many act to regulate transcription through a variety of mechanisms. lncRNAs can act as regulators of transcription by directly interacting with transcription factors as well as recruiting transcription complexes to specific promoters. For herpesviruses, several lncRNAs have now been identified including KSHV PAN RNA, human cytomegalovirus (HCMV) lncRNA4.9 and herpes simplex virus (HSV-1) LATs. However the full understanding of the role of herpesvirus encoded lncRNAs in infection is in its infancy. There is a critical need to define the function of herpesvirus lncRNAs and their contribution to virus replication and affects on cell gene expression.