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

项目总结 卡波西肉瘤相关疱疹病毒或人类疱疹病毒8型(KSHV/HHV8)是一种伽玛疱疹病毒 是导致卡波西肉瘤和体腔淋巴瘤的原因。在溶解的重新激活过程中，KSHV产生一个 高度丰富的核定位转录本，多腺化核RNA，PAN RNA。PAN RNA被证明是 调节病毒和细胞基因的表达。PAN RNA使用的一种机制涉及到 表观遗传修饰的变化。PAN RNA表达缺陷的重组BACmid未能 重新激活并产生上清液病毒。这确立了PAN RNA是一种必不可少的长非编码RNA (LncRNA)用于病毒复制和生长。 LncRNAs被定义为长度超过200个碱基的非蛋白质编码转录本。哺乳动物细胞中的incRNAs 数量非常丰富，估计有数万人，其中许多与疾病有关。 许多lncRNA现在已经被鉴定，并具有广泛的功能。许多人采取行动进行监管 通过各种机制转录。LncRNAs可直接作为转录调控因子 与转录因子相互作用，以及招募转录复合体到特定的启动子。为 疱疹病毒，目前已鉴定出几种lncRNA，包括KSHV PAN RNA，人类巨细胞病毒 (HCMV)lncRNA4.9和单纯疱疹病毒(HSV-1)LAT。然而，要充分认识到 疱疹病毒编码的lncRNA在感染中仍处于初级阶段。迫切需要定义的功能 疱疹病毒lncRNAs及其对病毒复制的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.