Non-coding RNAs in Gammaherpesvirus Infection and Disease

伽马疱疹病毒感染和疾病中的非编码 RNA

• 批准号: 9263885
• 负责人: Linda F. Van Dyk
• 金额: $ 38.54万
• 依托单位: UNIVERSITY OF COLORADO DENVER
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-04-19 至 2020-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9263885
• 关键词: AIDS related cancer; Acquired Immunodeficiency Syndrome; Acute; Address; Animal Model; Binding; Burkitt Lymphoma; Cells; Centers for Disease Control and Prevention (U.S.); Chronic; DNA Polymerase III; Defect; Disease; Disease Outcome; Disease model; Elements; Equilibrium; Foundations; Frequencies; Future; Gap Junctions; Gene Expression; Genetic; Genetic Transcription; Goals; HIV; HIV Infections; Herpesviridae; Highly Active Antiretroviral Therapy; Human; Human Herpesvirus 4; Human Herpesvirus 8; Hybrids; Immune; Immune Targeting; Immune response; Immunity; Immunosuppression; In Vitro; Incidence; Individual; Infection; Inflammatory; Intervention; Investigation; Kaposi Sarcoma; Knowledge; Large-Cell Immunoblastic Lymphoma; Link; Lysine-Specific tRNA; Malignant Neoplasms; Mediating; Methods; MicroRNAs; Mus; Nature; Neoplasms; Non-Hodgkin' s Lymphoma; Nucleic Acids; Pathogenesis; Pathology; Patients; Pneumonia; Process; Protein Biosynthesis; Proteins; Pulmonary Inflammation; RNA; RNA Polymerase III; RNA-Binding Proteins; Reagent; Regulation; Research Proposals; Risk; Role; Species Specificity; Specificity; Support System; System; Testing; Transfer RNA; Untranslated RNA; Viral; Viral Proteins; Virion; Virus; Virus Diseases; Virus Replication; base; cytokine; gammaherpesvirus; in vivo; interest; large cell Diffuse non-Hodgkin' s lymphoma; mutant; patient population; primary effusion lymphoma; public health relevance; recombinant virus; response; sarcoma; sensor; tripolyphosphate; tumorigenesis; virus host interaction

 DESCRIPTION (provided by applicant): Non-Coding RNAs In Gammaherpesvirus Infection And Disease The outcome of HV infection is strongly influenced by host immune control. Nowhere has this been more apparent than in HIV-infected individuals, and their increased propensity to develop malignancy. Two prime examples of this are Kaposis sarcoma and Non-Hodgkin lymphoma, HV- associated malignancies identified by the CDC as AIDS-defining illnesses. While these remain significant cancers in many parts of the world, their incidence in HIV-infected individuals has decreased in the era of highly-active antiretroviral therapy (HAART). While HAART has decreased the incidence of certain AIDS-associated neoplasms, individuals on HAART remain at risk for other HV-associated malignancies such as primary effusion lymphoma, Burkitt's lymphoma, plasmablastic lymphoma and diffuse large B cell lymphoma. Beyond tumorigenesis, HV infection is also associated with inflammatory pathologies in HIV-infected individuals, including AIDS-associated pneumonitis. While AIDS-associated immune suppression is thought to be a major contributor to uncontrolled chronic HV infection, it is likely that the immune and inflammatory dysregulation observed in HIV- infected individuals may impact HV pathogenesis in as yet undescribed ways. All HV analyzed to date express ncRNAs, including miRNAs. These RNAs have a significant potential to modify gene expression without encoding viral proteins that can be recognized and targeted by the immune response..The role of these ncRNAs during in vivo infection and pathogenesis remains unclear. HV68 is uniquely well-suited to address these gaps in knowledge, in providing a system that supports virus replication in vitro and allows analysis of the full course f infection in healthy and immune- suppressed hosts. We have studied the viral ncRNAs since our discovery of the gHV68 miRNAs, and we have an extensive set of reagents and expertise to address the function and mechanism of this ncRNAs. In this study, we will determine the effect of a number of ncRNA recombinant viruses in vivo, in healthy and immune deficient individuals. Further, we will determine the host interactors of the ncRNAs, and determine how HV infection modulates host ncRNAs and transcription. This investigation is likely to provide a foundation for a new nexus of virus/host interactions that is critical to the HVs and to HIV, and is a rich ground for future intervention.

 描述（由申请人提供）： γ 疱疹病毒感染和疾病中的非编码 RNA 宿主免疫控制对 HV 感染的结果的强烈影响在 HIV 感染者中表现得最为明显，而且他们患恶性肿瘤的可能性增加。这方面的两个主要例子是卡波西肉瘤和非霍奇金淋巴瘤，CDC 确定的与 HV 相关的恶性肿瘤为虽然这些疾病在世界许多地区仍然是重要的癌症，但在高效抗逆转录病毒治疗 (HAART) 时代，它们在艾滋病毒感染者中的发病率有所下降，而高效抗逆转录病毒治疗 (HAART) 则降低了某些艾滋病相关疾病的发病率。肿瘤，接受HAART的个体仍然面临其他与HV相关的恶性肿瘤的风险，例如原发性渗出性淋巴瘤、伯基特淋巴瘤、浆母细胞淋巴瘤和弥漫性大B细胞淋巴瘤。除了肿瘤发生之外，HV 感染还与 HIV 感染者的炎症病理有关，包括艾滋病相关肺炎，虽然艾滋病相关的免疫抑制被认为是不受控制的慢性 HV 感染的主要原因，但免疫系统很可能是导致这种疾病的主要原因。在 HIV 感染者中观察到的炎症失调可能以尚未描述的方式影响 HV 发病机制，迄今为止分析的所有 HV 都表达 ncRNA，包括 miRNA。 RNA 具有改变基因表达的巨大潜力，无需免疫反应识别和靶向的病毒编码蛋白。这些 ncRNA 在体内感染和发病机制中的作用仍不清楚 - HV68 非常适合解决这些空白。自从我们发现 gHV68 miRNA 以来，我们一直在研究病毒 ncRNA，并提供了一个支持病毒体外复制并允许分析健康和免疫抑制宿主的感染全过程的系统。一套广泛的试剂和专业知识来解决这种 ncRNA 的功能和机制。在这项研究中，我们将确定许多 ncRNA 重组病毒在健康和免疫缺陷个体体内的作用。此外，我们将确定宿主。 ncRNA 的相互作用，并确定 HV 感染如何调节宿主 ncRNA 和转录。这项研究可能为病毒/宿主相互作用的新关系奠定基础，这对病毒/宿主相互作用至关重要。 – HV 和 HIV，这是未来干预的丰富基础。