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，例如卡波西肉瘤相关疱疹病毒（KSHV；也称为 HHV8） 和鼠伽马疱疹病毒 68 (MHV-68) 是 DNA 病毒，在与宿主相互作用期间涉及潜伏和裂解程序，KSHV 感染会导致艾滋病定义的癌症，这代表了一个重大的临床问题，尽管 HAART 对卡波西肉瘤取得了积极的结果。关于这个角色知之甚少 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与病原体相互作用中的作用。除了适应性免疫之外，越来越明显的是，先天免疫在保护宿主生物体免受感染方面发挥着重要作用，以实现持续感染。与宿主共同进化，设计出成功复制和逃避宿主先天免疫系统的机制，MicroRNA (miRNA) 是 18-24 个核苷酸的单链。链状非编码 RNA，通常由基因转录物的非编码区域产生，通过碱基配对与靶 mRNA 结合，并指导这些靶 mRNA A 生长的转录后抑制。 最近的许多研究支持这样的假设：病毒编码 miRNA，帮助病毒逃避病毒 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，这可能是对病毒感染的先天免疫反应的一部分。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）在调节宿主和癌症之间相互作用中的作用。 MHV-68/KSHV 和逃避伽马疱疹病毒先天免疫机制，我们将采用高度创新、协作、多学科的方法以及最先进的核心设施的支持来解决新兴生物学领域的这些基本问题。