Alpha-herpesvirus assembly, egress and viral particle heterogeneity

α-疱疹病毒组装、流出和病毒颗粒异质性

• 批准号: 7878985
• 负责人: Gregory Allan Smith
• 金额: $ 6.56万
• 依托单位: NORTHWESTERN UNIVERSITY AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-01 至 2010-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7878985
• 关键词: Acyclovir; Address; Antiviral Agents; Blindness; Capsid; Capsid Proteins; Cell Nucleus; Cells; Comparative Study; Country; Coupled; Cytoplasm; Disease; Disease Progression; Encephalitis; Goals; Herpes zoster disease; Herpesviridae; Herpesvirus 1; Herpesvirus Type 3; Heterogeneity; Human; Human Herpesvirus 2; Individual; Infection; Intervention; Keratitis; Life; Link; Measures; Molecular; Morbidity - disease rate; Mutagenesis; Neonatal; Newborn Infant; Nuclear; Nuclear Envelope; Pathway interactions; Process; Property; Proteins; Role; Series; Simplexvirus; Staging; Structure; Study models; Subgroup; Suid Herpesvirus 1; Varicellovirus; Viral; Viral Pathogenesis; Viral Proteins; Virus; Virus Diseases; Viviparous-1 protein; X-Ray Crystallography; base; domain mapping; fluorescence imaging; imaging modality; member; mortality; mutant; novel strategies; particle; pathogen

The neuroinvasive herpesviruses are a highly-prevalent group of the alpha-herpesvirus subfamily that includes the human pathogens: herpes simplex virus types 1 and 2 (HSV-1, HSV-2), and varicella zoster virus (VZV). An additional member of this group is a virus of veterinary significance, pseudorabies virus (PRV), which historically has provided models for studying viral pathogenesis. Despite the availability of the antiviral compound acyclovir, several severe forms of disease caused by these viruses remain prevalent in this country and world wide. Infections associated with high rates of morbidity or mortality include encephalitis, keratitis, shingles and disseminated infections in newborns. Novel strategies to interfere with the assembly and egress of these viruses could prove valuable to treatment of infections, yet much of the herpesvirus infectious cycle remains undefined. In this application we leverage our expertise in infectious clone mutagenesis and single viral particle fluorescence imaging methods to dissect viral structural composition in living-cells and extracellularly, and to address the molecular pathways guiding viral assembly and egress. New evidence is provided indicating that the very large herpesvirus tegument protein, VP1/2, is a key effector of viral assembly during distinct stages of assembly in the nucleus and cytoplasm of infected cells. This proposal is based on the hypothesis that herpesvirus assembly and egress are coupled processes that occur through a series of sequential steps both in the nucleus and cytoplasm of infected cells, and that each of these steps are effected in part by the VP1/2 protein. Our goal is to refine our understanding of these steps at the level of the protein interactions that contribute to the dynamics of viral egress. This proposal includes comparative studies of model viruses from the two neuroinvasive herpesviruses subgroups, the simplexviruses (represented by HSV-1) and the varicelloviruses (represented by PRV), to develop a comprehensive analysis of the properties of these viruses.

神经侵袭性疱疹病毒是一种高度流行的α -疱疹病毒亚家族