Phenotypic analyses of HSV-1 miRNAs: H1, H6, & H8

HSV-1 miRNA 的表型分析：H1、H6、

• 批准号: 9760671
• 负责人: Enrico R. Barrozo
• 金额: $ 3.98万
• 依托单位: UNIVERSITY OF FLORIDA
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-08-16 至 2021-08-15
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9760671
• 关键词: Acute; Affect; Animal Model; Antiviral Agents; Biological; Biological Assay; Biological Models; Biological Process; Biology; Brain; Cell Culture Techniques; Cell Differentiation process; Cell Line; Cells; Chimera organism; Consequentialism; DNA biosynthesis; Data; Environment; Epithelium; Future; Gene Expression; Genes; Genome; Goals; Herpesviridae; Herpesviridae Infections; Herpesvirus 1; Human; Immune response; In Vitro; Individual; Infection; Innate Immune System; Latent Virus; Lead; Lethal Dose 50; Life; Location; Lytic; Measures; Messenger RNA; Methods; MicroRNAs; Modeling; Mus; Nature; Nervous system structure; Neuroblastoma; Neurons; Oryctolagus cuniculus; Pathogenesis; Phenotype; Play; Population; Primary Infection; RNA; RNA-Binding Proteins; RNA-Induced Silencing Complex; Research; Role; Simplexvirus; Site; Skin; Spinal Cord; Spinal Ganglia; Techniques; Testing; Time; Tissues; Training; Transcript; Translations; Travel; Untranslated RNA; Viral; Viral Genes; Virulence; Virus; Virus Diseases; Virus Latency; Virus Replication; Work; acute infection; career; crosslink; design; effective therapy; experimental study; in vivo; induced pluripotent stem cell; latency associated transcript; latent infection; lytic gene expression; mutant; nerve stem cell; neurovirulence; recombinant virus; relating to nervous system; sciatic nerve; viral RNA

Project Summary The majority of the human population is latently infected by herpes simplex virus type-1 (HSV-1), yet there are no effective therapies for clearing latent virus. During latency, the virus curbs lytic gene expression and only express a select few noncoding RNAs, including the latency associated transcript (LAT) and viral miRNAs. The biological functions of most HSV-1 miRNAs, in the context of viral infection, are largely unknown. Putative targets for HSV-1 miRNAs H1, H6, and H8 include viral and host transcripts. However, evidence for these mechanisms rely primarily on transient expression assays. Rigorous phenotypic analyses of recombinant viruses lacking individual miRNAs in cells relevant to HSV-1 biology and in vivo, in the context of viral infection, will elucidate the biological significance of these viral miRNA interactions in HSV-1 pathogenesis. Hypothesis: HSV-1 miRNAs H1, H6, & H8 will be found to facilitate HSV-1 lytic, latent, and/or recrudescent infections by fine-tuning the translation of viral and host transcripts. Since miRNAs repress translation, a virus lacking a miRNA that targets 1) a lytic gene, will increase virulence or 2) the host immune response, will decrease virulence. In addition, I may find that these miRNAs have multiple host or viral targets, that work synergistically or antagonistically to regulate the dynamic state of viral latency. Aim 1: Phenotypic & mechanistic analyses of miR-H1, H6, and H8 during acute infection in cell culture. Aim 2: Determine the effects of miR-H1, H6, and H8 on pathogenesis during acute infection in the mouse footpad infection model. Aim 3: Characterize the roles of miR-H1, H6, and H8 in latency and reactivation in murine dorsal root ganglia.

项目总结