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

• 批准号: 10328227
• 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
• 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/10328227
• 关键词: Advanced Development; Afferent Neurons; Alphaherpesvirinae; Animals; Antiviral Agents; Axonal Transport; 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; Life; Link; Malignant Neoplasms; Mass Spectrum Analysis; Medical; Methods; Modeling; Modification; Monitor; Morbidity - disease rate; Mothers; Mutagenesis; Nervous system structure; 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; base; defined contribution; design; human pathogen; in vivo; latent infection; mad itch virus; member; mortality; neonatal infection; nervous system infection; neuroproteomics; neurovirulence; novel; pathogen; programs; recombinant virus; relating to nervous system; repaired; tissue tropism; trait; vector; virus host interaction

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.

项目总结