Regulation of Gammaherpesviral Late Gene Expression

γ疱疹病毒晚期基因表达的调控

基本信息

批准号：
10223851
负责人：
Britt A Glaunsinger
金额：
$ 38.79万
依托单位：
UNIVERSITY OF CALIFORNIA BERKELEY
依托单位国家：
美国
项目类别：
财政年份：
2015
资助国家：
美国
起止时间：
2015-11-13 至 2026-02-28
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10223851
关键词：
Acquired Immunodeficiency Syndrome Antiviral Agents Architecture Area Binding Binding Proteins Biological Assay Biology C-terminal Cancer Etiology Cells Central Africa Complex Congenital Disorders Cytomegalovirus DNA Binding DNA Binding Domain DNA Polymerase II DNA Viruses DNA biosynthesis DNA replication origin DNA-Directed RNA Polymerase Data Disease Distal Double Stranded DNA Virus Enhancers Eukaryota Gene Activation Gene Expression Genes Genetic Transcription Genome Grant HIV Herpesviridae Human Human Herpesvirus 4 Human Herpesvirus 8 Hybrids Immunocompromised Host Individual Infection Late Gene Transcriptions Late Promoters Life Link Lytic Malignant Neoplasms Measures Modeling Molecular Mimicry Mutation N-terminal Oncogenic Patients Population Process Production Proteins Regulation Replication Origin Role TATA Box TATA-Box Binding Protein Testing Transcription Coactivator Transcription Initiation Transcriptional Regulation Viral Viral Genome Viral Proteins Virion Virus Virus Assembly Virus Replication cancer diagnosis experimental study gammaherpesvirus insight member mimicry mouse model mutation screening novel pathogen promoter recruit structural biology transcription factor viral DNA

项目摘要

ABSTRACT Herpesviruses are endemic within the human population, and cause a wide range of life-threatening diseases. Members of the betaherpesvirus and gammaherpesvirus subfamilies are extremely problematic in immunocompromised individuals, leading to severe congenital disorders and a variety of cancers. This proposal will define how a critical class of herpesviral genes are expressed late in the lifecycle of Kaposi's sarcoma-associated herpesvirus (KSHV) through a mechanism that involves a novel transcription complex, which combines both viral mimicry and co-option of select host machinery. The set of viral proteins required for late gene activation are broadly conserved among the beta- and gammaherpesviruses, indicating that information gained herein for KSHV will likely be applicable for Epstein-Barr virus and human cytomegalovirus as well. The focus of this grant is to define the composition and regulation of this novel gene expression complex, and reveal how its function is linked to viral genome replication. Given that even subtle mutations in this late gene transcription complex effectively `kill' the virus, an understanding of its composition and regulation is anticipated to reveal new targets for antiviral strategies.

抽象的疱疹病毒在人口中是流行的，并引起广泛的威胁生命的疾病。 Betaherpesvirus和Gammaherpesvirus亚家族的成员在免疫功能低下的个体，导致严重的先天性疾病和各种癌症。这提案将定义如何在Kaposi的生命周期中表达一系列关键类别的疱疹病毒基因通过涉及新型转录复合物的机制，与肉瘤相关的疱疹病毒（KSHV），结合了某些宿主机械的病毒模仿和合作。需要一组病毒蛋白晚期基因激活在β和γ瘤病毒中广泛保守，表明这里获得的KSHV的信息可能适用于爱泼斯坦 - 巴尔病毒和人类巨细胞病毒也是如此。该赠款的重点是定义这种新基因表达的组成和调节复杂，并揭示其功能如何与病毒基因组复制有关。鉴于这甚至微妙的突变该晚期基因转录复合物有效地“杀死”病毒，对其组成和预计法规将揭示抗病毒策略的新目标。