Tumorigenesis by the Epstein Barr Virus

EB 病毒引起的肿瘤发生

基本信息

批准号：
10696218
负责人：
NANCY JOAN RAAB-TRAUB
金额：
$ 34.72万
依托单位：
UNIV OF NORTH CAROLINA CHAPEL HILL
依托单位国家：
美国
项目类别：
财政年份：
1997
资助国家：
美国
起止时间：
1997-05-01 至 2027-06-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10696218
关键词：
Affect Agar Alternative Splicing Biological Assay Biological Process Bromodeoxyuridine Cell Line Cell physiology Cell secretion Cells ChIP-seq Coculture Techniques Collaborations CpG Islands DNA Deposition Development Epithelial Cells Epithelium Epstein-Barr Virus Infections Epstein-Barr Virus latency Exons Gene Cluster Gene Expression Gene Silencing Genes Genetic Transcription Genomics Goals Growth Human Herpesvirus 4 Human Papillomavirus Human papilloma virus infection Immunoprecipitation In Vitro Incidence Infection LMP1 Malignant Neoplasms Malignant neoplasm of cervix uteri Membrane Proteins Methylation MicroRNAs Migration Assay Mus NOD/SCID mouse Nuclear Pore Complex Oncogenic Oral Oropharyngeal Pathway interactions Population Process Production Property Protein Isoforms Protein Secretion Proteins RNA RNA Splicing Research Signal Pathway Small RNA Stains Structure Testing Throat Cancer Transcript Ubiquitination Untranslated RNA Viral Viral Genes Viral Oncogene Viral Proteins Virus Virus Diseases Visualization Western Blotting Xenograft procedure bisulfite sequencing cell growth co-infection exosome experimental study extracellular vesicles in vivo keratinocyte mRNA sequencing novel strategies opportunistic pathogen oral HPV oral infection permissiveness persistent EBV infection programs promoter transcriptome sequencing transforming virus tumor tumorigenesis uptake viral genomics virus related cancer whole genome

项目摘要

Project 4 Project Summary Abstract The goal of this project is to continue to determine how EBV modulates cell growth with particular focus on the BART long noncoding RNAs and to identify potential effects of the presence of EBV infected cells on the growth and expression of HPV infected cells. We have previously shown profound effects of the viral oncogenes, latent membrane proteins 1 and 2, on the growth of cells through activation of distinct signaling pathways and effects on protein levels through ubiquitination and determined that these proteins are secreted in exosomes and can be transferred to uninfected cells. Recently, we have utilized RNASeq to analyze total cellular expression in the AGS epithelial cell line, with or without EBV infection, grown in vitro and as tumors in NOD SCID mice in comparison with the C666 NPC cell line, and the NPC xenografts C15 and C17. The majority of the identified canonical pathways based on two fold changes in expression had decreased activity in vivo. EBV expression was also distinct with greatly increased transcription of the BART non coding RNAs in both NPC and the AGS cells. The significant expression of the viral BART nc RNAs in vivo in the absence of the EBV transforming proteins suggests that they are contributing factors to tumorigenesis. Their effects and potential mechanisms of action are a major focus of this application. EBV persistent infection in the oropharynx has several states of infection with cells that express multiple viral proteins including LMP1 and LMP2, cells that are restricted to BART miRNA and lnc RNA, and cells with some replicative reactivation. It is likely that through EV shedding, EBV may greatly impact other oropharyngeal viral infections. Importantly, HPV throat cancer is now the most rapidly increasing virally associated cancer. The almost universal oral infection with EBV could likely modulate the growth and cellular expression of HPV infected cells and potentially enhance their oncogenic properties. The in vivo interactions of EBV and HPV have not yet been defined. This proposal will determine how the distinct latent EBV infections or permissive infection alter the growth and expression of HPV infected cells.

项目4 项目摘要摘要该项目的目的是继续确定EBV如何调节细胞生长，特别关注 BART长期非编码RNA，并确定EBV感染细胞的存在的潜在影响 HPV感染细胞的生长和表达。我们以前已经显示出病毒的深刻作用癌基因，潜在的膜蛋白1和2，通过激活不同的信号传导来生长细胞的生长通过泛素化对蛋白质水平的途径和影响，并确定这些蛋白质是分泌的在外泌体中，可以转移到未感染的细胞中。最近，我们利用RNASEQ分析了总计 AGS上皮细胞系中的细胞表达，有或没有EBV感染，体外生长，作为肿瘤在与C666 NPC细胞系相比，NOD SCID小鼠以及NPC异种移植物C15和C17。这大多数基于表达的两倍变化的确定规范途径的活性降低了体内。 EBV表达也很明显，而BART非编码RNA的转录大大增加 NPC和AGS细胞。在没有的情况下，病毒BART NC RNA在体内的显着表达 EBV转化的蛋白质表明它们是肿瘤发生的因素。他们的影响和动作的潜在机制是该应用的主要重点。口咽中的EBV持续感染具有多种表达多重病毒的细胞感染状态包括LMP1和LMP2在内复制重新激活。 EBV可能会极大地影响其他口咽病毒感染。重要的是，HPV喉癌现在是病毒相关的癌症最快增加。这 EBV几乎普遍的口腔感染可能会调节HPV的生长和细胞表达感染的细胞并可能增强其致癌特性。 EBV和HPV的体内相互作用尚未定义。该建议将决定不同的潜在EBV感染或允许的方式感染改变了HPV感染细胞的生长和表达。