Virus-host interactions governing alpha-herpesvirus genome delivery and neuroinvasion

控制α-疱疹病毒基因组传递和神经侵袭的病毒-宿主相互作用

基本信息

批准号：
10569016
负责人：
GARY Edward PICKARD
金额：
$ 48.39万
依托单位：
NORTHWESTERN UNIVERSITY AT CHICAGO
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-02-01 至 2025-01-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10569016
关键词：
Advanced Development Afferent Neurons Alphaherpesvirinae Animals Antiviral Agents Axonal Transport Binding Binding Sites Biological Bite Brain Capsid Cell Culture Techniques Cell Nucleus Cells Cellular biology Complex DNA Viruses Data Disease Dsh protein Encephalitis Event Eye Family Family member Gene Delivery Genetic Genome Goals Herpes zoster disease Herpesviridae Herpesvirus 1 Herpesvirus Type 3 Human Herpesvirus 2 Immunocompetent Individual Infection Integration Host Factors Invaded Keratitis Link Malignant Neoplasms Maps Mass Spectrum Analysis Medical Methods Modeling Modification Monitor Morbidity - disease rate Mothers Mutagenesis Nervous System Neurons Newborn Infant Nuclear Oncolytic Pattern Peripheral Phenotype Phosphotransferases Positioning Attribute Property Protein Kinase Proteins Puncture procedure Recombinants Resources Rodent Role Simplexvirus Synapses Syringes Technology Tracer Trauma Vaccines Validation Varicellovirus Viral Viral Genome Viral Vector Virus Virus Diseases WNT Signaling Pathway Work defined contribution design human pathogen in vivo latent infection mad itch virus member mortality neonatal infection nervous system infection neural neuroproteomics neurovirulence novel pathogen permissiveness programs recombinant virus repaired tissue tropism trait ubiquitin isopeptidase vector virus host interaction

项目摘要

PROJECT SUMMARY Spread of neuroinvasive herpesviruses from sensory neurons to the eye, brain, or from mother to newborn, are significant causes of morbidity and mortality. Herpes simplex virus type 1 (HSV1) and pseudorabies virus (PRV) are representative members of the two genuses of mammalian neuroinvasive herpesviruses (simplexviruses & varicelloviruses). These viruses are dependent upon spread to the nervous system to establish life-long latent infections, yet very little is known regarding the neuroinvasive mechanism that underlies this remarkable trait. We propose to study the virus neuroinvasive machinery with the intent to: (i) decipher how these viruses invade the nervous system, (ii) understand the intrinsic barriers to neural infection that these viruses evade, and (iii) produce and characterize viruses lacking the neuroinvasive property as potential vaccines and recombinant vectors. These studies are designed to identify the virus-cellular interactions that promote virus genome delivery to the nuclei of non-neuronal and neuronal cells, and the corresponding intrinsic defenses that keep most pathogens at bay. We include preliminary data demonstrating that this path-breaking collaborative study has far-reaching medical and biological implications.

项目摘要神经侵袭性疱疹病毒从感觉神经元到眼睛，大脑或从母亲到母亲传播新生儿是发病率和死亡率的重要原因。单纯疱疹病毒1型（HSV1）和伪标记病毒（PRV）是哺乳动物两个属的代表成员神经活动性疱疹病毒（单纯病毒和杂质病毒）。这些病毒取决于传播到神经系统以建立终身潜在感染，但关于这种非凡特征的基础的神经侵染机制。我们建议研究病毒神经活动机制的目的是：（i）这些病毒如何侵入神经系统，（ii）了解这些病毒逃避的神经感染的内在障碍，并且（iii）产生和将缺乏神经侵染特性的病毒作为潜在的疫苗和重组载体。这些研究旨在识别促进病毒基因组递送的病毒细胞相互作用到非神经元和神经元细胞的核，以及相应的内在防御措施大多数病原体在海湾。我们包括初步数据，证明了这种破裂的协作研究具有深远的医学和生物学意义。