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

非编码 RNA 在调节 γ-疱疹病毒-宿主相互作用中的作用

• 批准号: 8660815
• 负责人: TARIQ M RANA
• 金额: $ 44.3万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-09-19 至 2019-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8660815
• 关键词: Acquired Immunodeficiency Syndrome; Address; Animal Model; Animals; Antiviral Agents; Base Pairing; Binding; Biological Models; Biology; Cancer Vaccines; Cell Culture Techniques; Cells; Clinical; Collaborations; Complex; Core Facility; DNA Viruses; Development; Disease Progression; Functional RNA; Genes; Goals; Herpesviridae; Herpesviridae Infections; Highly Active Antiretroviral Therapy; Human; Human Herpesvirus 8; Immune; Immune response; Immune system; Immunity; In Vitro; Infection; Invaded; Kaposi Sarcoma; Laboratories; Life Cycle Stages; Lung; Lytic; Malignant Neoplasms; Mediating; Messenger RNA; MicroRNAs; Mus; Natural Immunity; Nucleotides; Organism; Outcome; Phase; Play; RNA; RNA Interference; Regulation; Repression; Role; Small RNA; Technology; The Sun; Time; Transcript; Vaccines; Validation; Viral; Virus; Virus Diseases; Virus Latency; Work; adaptive immunity; base; cell type; design; gammaherpesvirus; in vivo; inhibitor/antagonist; innovation; innovative technologies; insight; interdisciplinary approach; lytic replication; mRNA Expression; microbial; nanoparticle; pathogen; programs; recombinant virus; research study; response; tumor; validation studies; virus host interaction

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.

γ-疱疹病毒，如卡波西肉瘤相关疱疹病毒（KSHV;也称为HHV 8） 和鼠γ疱疹病毒68（MHV-68）是在与宿主相互作用期间涉及潜伏和裂解程序的DNA病毒。KSHV感染导致代表重要临床问题的AIDS定义癌症。尽管HAART对卡波西肉瘤有积极的疗效， KSHV特异性宿主免疫在疾病进展中的作用。该项目的主要目标是了解非编码RNA在调节γ-疱疹病毒生命周期和调节宿主-病原体相互作用中的作用。人类宿主被广泛的微生物病原体入侵，并进化出许多防御机制来生存这些感染。除了适应性免疫之外，越来越清楚的是，先天免疫在保护宿主生物体免受感染方面起着重要作用。为了实现持续感染，病原体与宿主共同进化以设计成功复制和逃避宿主先天免疫系统的机制。microRNA（miRNAs）是一种长度为18-24个核苷酸的单链非编码RNA，通常产生于基因转录物的非编码区，通过碱基配对与靶mRNA结合，并引导这些靶mRNA的转录后抑制。越来越 最近的一些研究支持病毒编码帮助病毒逃避的miRNAs的假设， 感染细胞的免疫反应和调节病毒生命周期的不同阶段。除了病毒miRNA之外，最近的研究表明，宿主细胞通过改变细胞miRNA的表达来响应病毒感染，所述细胞miRNA可能是对病毒感染的先天免疫应答的一部分。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复合物（包括RNAi机制）在调节宿主与MHV-68/KSHV之间的相互作用以及逃避γ疱疹病毒先天免疫机制中的作用。我们将采用高度创新，协作，多学科的方法，并从最先进的核心设施的状态支持，以解决这些基本问题，在生物学的新兴领域。