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Mechanisms mediating HCMV genome maintenance during latency

潜伏期介导 HCMV 基因组维持的机制

基本信息

批准号：
9243910
负责人：
Laura Hertel
金额：
$ 40.88万
依托单位：
CHILDREN'S HOSPITAL & RES CTR AT OAKLAND
依托单位国家：
美国
项目类别：
财政年份：
2013
资助国家：
美国
起止时间：
2013-04-15 至 2019-11-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9243910
关键词：
Acquired Immunodeficiency Syndrome Advanced Development Alpha Cell Antiviral Therapy B-Lymphocytes Biological Assay Blood Bone Marrow CD34 gene Cells Child Chromosomes Cis-Acting Sequence Computer software Cytomegalovirus Cytomegalovirus Infections DNA-Directed DNA Polymerase Deoxyuridine Development Disease Economic Burden Ensure Episome Epstein-Barr Virus latency Event Fibroblasts Fluorescent in Situ Hybridization Foundations Genetic Complementation Test Genome Genomics Goals Harvest Hematopoietic Hematopoietic stem cells Herpesviridae Human Human Herpesvirus 8 Immunocompromised Host Individual Infection Innovative Therapy Knowledge Label Libraries Life Light Maintenance Mediating Metaphase Plate Monitor Morbidity - disease rate Myeloid Cells Myeloid Progenitor Cells Newborn Infant Orthophosphate Patients Peripheral Plasmids Population Primary Infection Process Production Proliferating Research Source Southwestern Blotting Testing Time Tissues Transplant Recipients Vaccines Viral Viral Genome Virion Virus Virus Inhibitors Virus Latency Work cell type daughter cell disability experimental study health economics in vitro Model insight interest mathematical model mortality mutant novel novel therapeutics public health relevance screening self-renewal theories vector viral DNA

项目摘要

DESCRIPTION (provided by applicant): Human cytomegalovirus (CMV) infections are a substantial source of morbidity and mortality in transplant recipients, and a major cause of long-term disabilities in congenitally infected children. Because of this, the development of new antiviral therapies is urgently needed. The ability of this virus to undergo lifelong latency and reactivation cycles, however, represents a formidable obstacle in our progress towards this goal. Here, we propose to use two in vitro models of CMV latency in hematopoietic cells to conclusively establish if and how maintenance of latent viral genomes is achieved in dividing myeloid progenitor cells. This work will provide significant insights into a crucial aspect of CMV latency, and will constitute the foundation for the development of innovative therapies with the potential to eradicate this virus from the human population.

描述（由申请人提供）：人巨细胞病毒（CMV）感染是移植受者发病率和死亡率的重要来源，也是先天性感染儿童长期残疾的主要原因。因此，迫切需要开发新的抗病毒疗法。然而，这种病毒经历终身潜伏和再激活周期的能力是我们实现这一目标的一个巨大障碍。在这里，我们建议使用两种体外造血细胞CMV潜伏期模型来最终确定是否以及如何在骨髓祖细胞分裂中实现潜伏病毒基因组的维持。这项工作将为巨细胞病毒潜伏期的一个关键方面提供重要的见解，并将为开发有可能从人群中根除这种病毒的创新疗法奠定基础。