Tegument Envelope Protein Interactions in CMV Envelopment

CMV 包膜中的皮膜包膜蛋白相互作用

• 批准号: 10573700
• 负责人: William Jarvis Britt
• 金额: $ 49.61万
• 依托单位: UNIVERSITY OF ALABAMA AT BIRMINGHAM
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-11-08 至 2027-10-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10573700
• 关键词: Acute; Antiviral Therapy; Biochemistry; Capsid; Cell membrane; Cells; Cellular Membrane; Child; Complex; Cryoelectron Microscopy; Cytomegalovirus; Cytomegalovirus Infections; Cytoplasm; Data; Dose Limiting; Endosomes; Ensure; Generations; Glycoproteins; Goals; Golgi Apparatus; Herpesviridae; Human; Image; Immunocompromised Host; Individual; Infant; Licensing; Lipids; Malignant - descriptor; Membrane; Membrane Protein Traffic; Metabolic; Microtubule-Organizing Center; Microtubules; Modification; Morbidity - disease rate; Morphogenesis; Mutation; Pathway interactions; Phenotype; Post-Translational Protein Processing; Production; Proteins; Recycling; Reporting; Role; Site; Stress; Structural Protein; Structure; Testing; Therapeutic Agents; Toxic effect; Vaccines; Vacuole; Viral; Viral Proteins; Virion; Virus; Virus Assembly; Virus Diseases; Virus Replication; antiviral drug development; env Gene Products; in utero; interest; mortality; mutant; novel; particle; protein protein interaction; protein transport; recombinant virus; response; stoichiometry; therapeutic development; trafficking; trans-Golgi Network; vaccine strategy

Human cytomegalovirus (HCMV) is responsible for significant mortality and morbidity in immunocompromised patients and results in neurodevelopmental abnormalities in infants and children infected in-utero. Currently there is no licensed vaccine and antiviral therapies have dose limiting toxicities. Thus, further understanding of the replication of this virus, including mechanisms of virion envelopment, could identify new strategies for vaccine and antiviral drug development. In this proposal, we will define interactions between an essential virion glycoprotein complex, gM/gN, and membrane associated outer tegument proteins that lead to envelopment of the virus in a specialized cellular compartment, the assembly compartment. Recombinant viruses with specific mutations in envelope and outer tegument proteins that result in shared phenotypes of defective envelopment will be used to define of viral glycoprotein/ tegument protein interactions required for virion assembly. In addition to increasing current understanding of herpesvirus assembly, results from these studies could potentially identify novel targets for development of therapeutics to limit replication of this virus.

人巨细胞病毒（HCMV）是导致免疫功能低下患者显著死亡率和发病率的原因，并导致宫内感染的婴儿和儿童神经发育异常。目前还没有获得许可的疫苗，抗病毒治疗具有剂量限制性毒性。因此，进一步了解这种病毒的复制，包括病毒粒子包裹机制，可以确定疫苗和抗病毒药物开发的新策略。在这个提议中，我们将定义一个必要的病毒体糖蛋白复合物，gM/gN，和膜相关的外层蛋白，导致病毒在一个专门的细胞室，组装室的deliment之间的相互作用。将使用在包膜和外被膜蛋白中具有导致缺陷性表达的共同表型的特定突变的重组病毒来定义病毒体组装所需的病毒糖蛋白/被膜蛋白相互作用。除了增加目前对疱疹病毒组装的理解外，这些研究的结果可能会发现新的靶点，用于开发限制这种病毒复制的治疗方法。