Regulation of Gammaherpesviral Late Gene Expression

γ疱疹病毒晚期基因表达的调控

• 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
• 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

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.

摘要 疱疹病毒在人群中是地方性的，并且引起广泛的威胁生命的疾病。 β疱疹病毒和γ疱疹病毒亚家族的成员在感染中存在极大的问题。 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 一项提案将定义一类关键的疱疹病毒基因是如何在卡波济氏病的生命周期后期表达的。 肉瘤相关疱疹病毒（KSHV）通过一种涉及新的转录复合物的机制， 其结合了病毒模拟和选择宿主机制的共选择。一组病毒蛋白需要 晚期基因激活在β和γ疱疹病毒中广泛保守，表明 本文获得的KSHV信息可能适用于EB病毒和人巨细胞病毒 也这项资助的重点是确定这种新基因表达的组成和调控 复杂，并揭示其功能如何与病毒基因组复制相关联。即使是微小的突变， 这种晚期基因转录复合物有效地“杀死"病毒，了解其组成， 预期调控将揭示抗病毒策略的新靶点。