Role of Non-Coding RNAs in Regulating Gamma-Herpesvirus-Host-Interactions

伽玛疱疹病毒，如卡波西肉瘤相关疱疹病毒(KSHV；也称为HHV8) 而小鼠疱疹病毒68(MHV-68)是一种DNA病毒，在与宿主的相互作用中既涉及潜伏程序，又涉及裂解程序。KSHV感染导致艾滋病定义癌症，这是一个重大的临床问题。尽管HAART治疗卡波西肉瘤取得了积极的结果，但人们对其作用知之甚少 KSHV特异性宿主免疫在疾病进展中的作用。这个项目的主要目标是了解非编码RNA在调节伽玛-疱疹病毒生命周期和调节宿主-病原体相互作用中的作用。人类宿主受到广泛的微生物病原体的入侵，并进化出了许多防御机制来在这些感染中生存下来。除了获得性免疫外，越来越清楚的是，天然免疫在保护宿主免受感染方面发挥着重要作用。为了实现持续感染，病原体与宿主共同进化，设计出成功复制和逃避宿主天然免疫系统的机制。MicroRNAs(MiRNAs)是由基因转录物的非编码区产生的18-24个核苷酸的单链�非编码区，通过碱基配对与靶mRNAs结合，并指导这些靶mRNAs的转录后抑制。一个不断增长的 最近的一些研究支持病毒编码帮助病毒逃避的miRNAs的假设 感染细胞中的免疫反应，并调节病毒生命周期的不同阶段。除了病毒miRNAs，最近的研究表明，宿主细胞对病毒感染的反应是通过改变细胞miRNAs的表达来实现的，这可能是对病毒感染的先天性免疫反应的一部分。了解基于RNA的增强免疫系统的机制将直接影响抗病毒和癌症疫苗的新策略的设计。我们的项目将研究宿主非编码RNA和RNP复合体，包括RNAi机制在调节宿主与MHV-68/KSHV之间的相互作用和逃避伽马疱疹病毒天然免疫机制中的作用。我们将采用高度创新、协作、多学科的方法，并得到最先进的核心设施的支持，以解决新兴生物学领域的这些基本问题。

Gamma -herpesviruses such as Kaposi's sarcoma-associated herpesvirus (KSHV; also known as HHV8) and murine gamma herpesvirus 68 (MHV-68) are DNA viruses involving both latent and lytic programs during their interactions with host. KSHV infection leads to an AIDS defining cancer that represents a significant clinical problem. Despite the positive outcome of HAART on Kaposi Sarcoma, little is known about the role of KSHV-specific host immunity in disease progression. The main goal of this project is to understand the role of non-coding RNAs in modulating gamma-herpesvirus life cycle and in regulating host-pathogen interactions. The human host is invaded by a wide range of microbial pathogens and has evolved a number of defensive mechanisms to survive these infections. In addition to adaptive immunity, it is becoming increasingly clear that innate immunity plays an important role in protecting host organisms from infections. To achieve persistent infections, pathogens have co-evolved with host to devise mechanisms to successfully replicate and evade host innate immune system. MicroRNAs (miRNAs) are 18-24 nucleotide single� stranded non-coding RNA, usually generated from noncoding regions of gene transcripts, bind to target mRNAs by base-pairing, and guide posttranscriptional repression of these target mRNAs. A growing number of recent studies support the hypothesis that viruses encode miRNAs that assist viruses to evade immune responses in infected cells and to regulate different phases of viral life cycle. In addition to viral miRNAs, recent studies show that host cells respond to viral infections by changing the expression of cellular miRNAs that could be a part of innate immune response to viral infections. Understanding the RNA-based mechanisms to boost immune system will directly impact the design of new strategies for antiviral and cancer vaccines. Our project will investigate the role of host non-coding RNAs and RNP complexes including RNAi machinery in regulating interactions between a host and MHV-68/KSHV and in evading gammaherpesvirus innate immune mechanisms. We will employ highly innovative, collaborative, multidisciplinary approaches, and support from state of the art cores facilities to address these fundamental questions in an emerging field of biology.