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Cellular DNAJ Proteins and SV40 Infection

细胞 DNAJ 蛋白和 SV40 感染

基本信息

批准号：
8307757
负责人：
Daniel C. Dimaio
金额：
$ 24.61万
依托单位：
YALE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2011
资助国家：
美国
起止时间：
2011-07-01 至 2014-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8307757
关键词：
BK Virus Binding Biochemical Biological Cancer Patient Capsid Cell surface Cells Collaborations Disease Escape Mutant Event Family Family member Funding Gene Expression Gene Family Genes Genetic Genetic Screening Grant Head Human Human Herpesvirus 4 Human Virus Human papillomavirus 18 Individual Infection Large T Antigen Lead Molecular Molecular Chaperones Monkeys Oncogenic Viruses Papillomavirus Play Polyomavirus Polyomavirus Infections Process Property Proteins Relative (related person)Repression Role Series Signal Transduction Simian virus 40 Technology Testing Transmembrane Transport Tumor Virus Infections Viral Virus Virus Diseases base cellular targeting immunosuppressed insight knock-down member metaplastic cell transformation mutant novel novel strategies prevent reconstitution research study response senescence small hairpin RNA trafficking

项目摘要

This new project headed by Dr. DiMaio is based on a discovery made in project 2 during the current funding period. The polyomaviruses, BK virus andJC virus, cause serious diseases in immunosuppressed individuals including cancer patients and, like their close relative SV40, are putative human tumor viruses. With the support of this grant, we discovered that the cellular co-chaperones DNAJ-B12 and DNAJ-B14 are required for efficient infection by these three viruses. When expression of these genes is repressed by shRNAs, there is a substantial reduction in expression of the major early protein, large T antigen. Virus binding to the cell surface appears unimpaired, suggesting that the DNAJ-B12/14 sensitive step(s) is in some aspect of virus entry, intracellular trafficking, or uncoating. We will conduct a series of biochemical, cell biological and genetic studies to elucidate the mechanistic role played by DNAJ-B12/14 in SV40 infection. We will determine how far infection proceeds in cells lacking DNAJ-B12/14 function, and determine what step in the virus entry/trafficking/uncoating process is blocked. We will conduct mutational and biochemical analysis of DNAJ-B12/14 to determine its mode of action at the molecular level. Viral escape mutants that allow infection despite DNAJ-B12/14 repression will be isolated and characterized. Finally, we will use shRNA technology to determine whether other members of the DNAJ gene family are required for infection by the polyomaviruses and other viruses, including Epstein-Barr virus in collaboration with Dr. Miller. These experiments will provide new insights into the process of tumor virus infection and characterize the role of new putative anti-viral targets.

diaio博士领导的这个新项目是基于当前项目2的发现