ROLE OF CELL INTEGRINS IN ADENOVIRAL CONJUNCTIVITIS

细胞整合素在腺病毒结膜炎中的作用

基本信息

批准号：
8266469
负责人：
Glen R Nemerow
金额：
$ 45.58万
依托单位：
SCRIPPS RESEARCH INSTITUTE, THE
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：
1997-01-01 至 2014-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8266469
关键词：
Acute respiratory infection Adenovirus Infections Adenoviruses Affinity Antiviral Agents Basic Science Binding Binding Sites Biochemical Capsid Capsid Proteins Cells Cellular Structures Chimera organism Clinical Research Complex Conjunctivitis Cryoelectron Microscopy Defensins Development Disease Epidemic Keratoconjunctivitis Eye Eye Infections Frequencies Funding Gastrointestinal tract structure Goals HDAC5 gene Human Adenovirus Infections Human Adenoviruses Human Papillomavirus Immune Immune system Immunocompromised Host In Vitro Infection Integrins Investigation Knowledge Lead Libraries Lysosomes Medical Molecular Morbidity - disease rate Pathway interactions Peptides Play Property Proteins Resistance Role Site Structure Surface Plasmon Resonance Therapeutic Time Viral Virion Virus Visual Acuity X ray diffraction analysis X-Ray Diffraction abstracting adenovirus penton protein antimicrobial peptide base combinatorial effective therapy high throughput screening human neutrophil peptide 1 improved insight late endosome microbial multidisciplinary novel pathogen prevent small molecule small molecule libraries stoichiometry three dimensional structure

项目摘要

Project Summary/Abstract Human adenoviruses are major causes of acute infections of the respiratory, gastrointestinal tract, and the eye. In severe cases of ocular infections, such as those occurring in epidemic keratoconjunctivitis, adenovirus can cause significant morbidity and loss of visual acuity. At the present time, there are few if any effective antiviral agents that have been approved for the treatment of adenovirus eye infections. The studies proposed here seek to remedy this situation by capitalizing on the significant progress made during the previous funding period as well as our new preliminary studies. Specifically, we propose to undertake a systematic and multidisciplinary investigation of the antiviral activities of naturally occurring antimicrobial peptides (AMPs) and novel synthetic small molecules. The major goal of the proposed studies is to determine precisely how AMPs and synthetic small molecules intervene in the adenovirus cell entry pathway. This goal will be achieved by: 1) identifying the adenoviral coat proteins that are recognized by AMPs and synthetic molecules; 2) analyzing the precise adenovirus binding properties of AMPs; 3) solving the three-dimensional structure of adenovirus-AMP complexes by X-ray diffraction and cryoelectron microscopy; and 4) employing high-throughput screens of combinatorial libraries to discover novel synthetic small molecules that restrict adenovirus infection. These investigations should not only improve our knowledge of adenovirus structure and the mechanisms involved in host cell entry but could also lead to the development of new treatments for adenovirus-induced ocular diseases.

项目概要/摘要人类腺病毒是引起呼吸道、胃肠道、和眼睛。在眼部感染严重的情况下，例如流行病中发生的情况角结膜炎、腺病毒可导致显着的发病率和视力丧失。在目前，很少有有效的抗病毒药物被批准用于治疗腺病毒眼部感染。这里提出的研究试图通过利用关于上一个资助期间取得的重大进展以及我们新的初步进展研究。具体来说，我们建议对这一问题进行系统的、多学科的调查。天然存在的抗菌肽（AMP）和新型合成小分子的抗病毒活性分子。拟议研究的主要目标是准确确定 AMP 和合成小分子干预腺病毒细胞进入途径。这一目标将通过以下方式实现： 1) 鉴定被 AMP 和合成分子识别的腺病毒外壳蛋白； 2）分析AMP精确的腺病毒结合特性； 3）求解三维通过 X 射线衍射和冷冻电子显微镜观察腺病毒-AMP 复合物的结构；和 4）利用组合文库的高通量筛选来发现新型合成小分子限制腺病毒感染的分子。这些调查不仅应该改善我们的了解腺病毒结构和参与宿主细胞进入的机制，但也可能导致开发腺病毒引起的眼部疾病的新疗法。

项目成果

期刊论文数量（46）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Crystal structure of human adenovirus at 3.5 A resolution.

DOI：
10.1126/science.1187292
发表时间：
2010-08-27
期刊：
Science (New York, N.Y.)
影响因子：
0
作者：
Reddy VS;Natchiar SK;Stewart PL;Nemerow GR
通讯作者：
Nemerow GR

Crystallization and preliminary X-ray diffraction analysis of human adenovirus.

DOI：
10.1016/j.virol.2010.03.028
发表时间：
2010-06-20
期刊：
Virology
影响因子：
3.7
作者：
Reddy VS;Natchiar SK;Gritton L;Mullen TM;Stewart PL;Nemerow GR
通讯作者：
Nemerow GR

Insights into adenovirus host cell interactions from structural studies.

DOI：
10.1016/j.virol.2008.10.016
发表时间：
2009-02-20
期刊：
VIROLOGY
影响因子：
3.7
作者：
Nemerow, G. R.;Pache, L.;Reddy, V.;Stewart, P. L.
通讯作者：
Stewart, P. L.

Switch from capsid protein import to adenovirus assembly by cleavage of nuclear transport signals.

通过裂解核转运信号从衣壳蛋白输入转变为腺病毒组装。

DOI：
10.1093/emboj/cdg614
发表时间：
2003
期刊：
The EMBO journal.
影响因子：
0
作者：
Wodrich,Harald;Guan,Tinglu;Cingolani,Gino;VonSeggern,Dan;Nemerow,Glen;Gerace,Larry
通讯作者：
Gerace,Larry

Conservation of fiber structure and CD46 usage by subgroup B2 adenoviruses.