HCMV Glycoprotein B-Induced A Signal Pathway

HCMV 糖蛋白 B 诱导的 A 信号通路

• 批准号: 7046852
• 负责人: HUA ZHU
• 金额: $ 26.57万
• 依托单位: UNIV OF MED/DENT OF NJ-NJ MEDICAL SCHOOL
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-09-01 至 2008-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7046852
• 关键词: DNA binding protein; biological signal transduction; cytomegalovirus; gene induction /repression; genetic library; host organism interaction; interferons; regulatory gene; virus protein

DESCRIPTION (provided by applicant): Human cytomegalovirus (HCMV) is a ubiquitous human pathogen. It is a major cause of infectious morbidity and mortality in immunocompromised individuals, especially in transplant recipients and AIDS patients. It is also a leading cause of congenital birth defects. My long-term research goal is to elucidate the interactions of HCMV with Its host cell at the molecular level, and evaluate the consequences of these interactions, especially the effects on viral replication and pathogenesis. In this proposal, I will focus on the significance of the induction of interferon-stimulated genes (ISGs) following HCMV infection. My specific aims are as follows: I. Identify HCMV-response elements (HCRE)-binding proteins. Two elements, the interferon stimulated element (ISRE) and gamma-interferon activated site (GAS), have been identified responsible for HCMV-mediated ISG induction. Gel shift assays have shown that four protein complexes interact with these elements. Identification of the consensus sequence of HCRE and HCRE-binding proteins are critical for understanding molecular basis of this signal transduction pathway. I propose different experiments to approach these questions, including: (1) Test base-pair substitutions to identify the sequence motifs necessary for HCMV-mediated ISG induction. (2) Examine known HCRE-binding proteins in the interferon regulatory factor family for their roles in HCMV-mediated signal transduction pathway. (3) Purify HCRE-binding proteins by chromatography and identify these binding proteins by 2-dimensional electrophoresis and mass spectrometric analysis. (4) Screen HCRE-binding proteins using a yeast one-hybrid system. (5) Screen HCRE-binding proteins using retrovirus cDNA expression libraries. II. To investigate biological significance of the induction of ISGs by HCMV infection. HCMV envelope glycoprotein B (gB) has been identified for initiating this signal transduction pathway. Importance of initiating this signal pathway in HCMV replication will be studied using biochemical and genetic approaches, including: (1) The roles of HCMV activated proteins in the induction of ISGs and HCMV IE genes will be studied. (2) Mutate two GAS elements in the HCMV major IE promoter and examine their roles in viral gene expression and replication.

描述（申请人提供）：人类巨细胞病毒（HCMV）是一种普遍存在的人类病原体。它是免疫功能低下个体，特别是移植受者和艾滋病患者感染性发病率和死亡率的主要原因。它也是先天性出生缺陷的主要原因。我的长期研究目标是在分子水平上阐明HCMV与宿主细胞的相互作用，并评估这些相互作用的后果，特别是对病毒复制和发病机制的影响。在本提案中，我将重点关注HCMV感染后干扰素刺激基因（ISGs）诱导的意义。我的具体目标如下：

项目成果

Using DNA microarray to study human cytomegalovirus gene expression.

使用DNA微阵列研究人类巨细胞病毒基因表达。

• DOI: 10.1016/j.jviromet.2005.08.014
• 发表时间: 2006
• 期刊: Journal of virological methods.
• 作者: Yang,Shaojun;Ghanny,Saleena;Wang,Weijia;Galante,Anthony;Dunn,Walter;Liu,Fenyong;Soteropoulos,Patricia;Zhu,Hua
• 通讯作者: Zhu,Hua

Accurate identification of non-polyadenylated RNA using a custom human cytomegalovirus tiling array.

使用定制的人巨细胞病毒平铺阵列准确鉴定非聚腺苷酸化 RNA。

• DOI: 10.1016/j.jviromet.2012.09.020
• 发表时间: 2013
• 期刊: Journal of virological methods
• 影响因子: 3.1
• 作者: Huang,Ying;Warden,Charles;Zhu,Hua
• 通讯作者: Zhu,Hua

Development of a gene capture method to rescue a large deletion mutant of human cytomegalovirus.

开发一种基因捕获方法来拯救人类巨细胞病毒的大缺失突变体。

• DOI: 10.1016/j.jviromet.2008.12.021
• 发表时间: 2009
• 期刊: Journal of virological methods
• 影响因子: 3.1
• 作者: Dulal,Kalpana;Zhang,Zhen;Zhu,Hua
• 通讯作者: Zhu,Hua

Genome-wide mutagenesis reveals that ORF7 is a novel VZV skin-tropic factor.

• DOI: 10.1371/journal.ppat.1000971
• 发表时间: 2010-07-01
• 期刊: PLoS pathogens
• 影响因子: 6.7
• 作者: Zhang Z;Selariu A;Warden C;Huang G;Huang Y;Zaccheus O;Cheng T;Xia N;Zhu H
• 通讯作者: Zhu H

Two gamma interferon-activated site-like elements in the human cytomegalovirus major immediate-early promoter/enhancer are important for viral replication.

人巨细胞病毒主要立即早期启动子/增强子中的两个γ干扰素激活的位点样元件对于病毒复制很重要。

• DOI: 10.1128/jvi.79.8.5035-5046.2005
• 发表时间: 2005
• 期刊: Journal of virology.
• 作者: Netterwald,James;Yang,Shaojun;Wang,Weijia;Ghanny,Salena;Cody,Michael;Soteropoulos,Patricia;Tian,Bin;Dunn,Walter;Liu,Fenyong;Zhu,Hua
• 通讯作者: Zhu,Hua