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dc.contributorNot Applicableen_US
dc.contributor.authorRUYECHAN, WILLIAM T Principal Investigatoren_US
dc.date31-Aug-11en_US
dc.date2009en_US
dc.date.accessioned2011-04-18T20:59:25Zen_US
dc.date.accessioned2011-04-19T18:31:03Z
dc.date.available22-Sep-09en_US
dc.date.available2011-04-18T20:59:25Zen_US
dc.date.available2011-04-19T18:31:03Z
dc.date.issued2011-04-18T20:59:25Zen_US
dc.identifier7920666en_US
dc.identifier3R56AI018449-25A2S1en_US
dc.identifier18449en_US
dc.identifier.urihttp://hdl.handle.net/10477/1043
dc.descriptionAffinity;Attenuated;Attenuated Vaccines;attenuation;base;Binding (Molecular Function);Binding Sites;Biological Assay;Cell physiology;Cells;Chickenpox;Child;Clinical Trials;Complex;Consensus;Data;Development;dimer;Dimerization;DNA;DNA Binding;DNA Binding Domain;DNA Polymerase II;domain mapping;Elderly;Elements;EMSA;FDA approved;Funding;Gene Expression;Generations;Genes;Genetic Transcription;Growth;Herpes zoster disease;Human;Human herpesvirus 3;In Vitro;in vitro Assay;Infection;Lead;Life;Maps;Mediating;Mediator of activation protein;model development;Modeling;Molecular;mutant;Mutate;Mutation;Nature;Pathogenesis;PC4 Gene;Pharmaceutical Preparations;Population;prevent;Prevention;Promotor (Genetics);Property;Protein Analysis;Proteins;Recombinants;Regulation;Reporter;Reporter Genes;research study;Role;Serine;Site;Site-Directed Mutagenesis;Specificity;Structure;Trans-Activation (Genetics);Trans-Activators;Transcript;Transcription Coactivator;transcription factor;Transcription Initiation;Transcriptional Activation;Transcriptional Activation Domain;Vaccination;Vaccines;Varicella-Zoster immediate early virus;Viral;viral DNA;Viral Genes;Viral Genome;Viral Proteins;Virus;Virus Diseases;Virus Replication;Work;yeast two hybrid system;Yeasts;en_US
dc.descriptionAmount: $ 394857en_US
dc.description.abstractVaricella zoster virus (VZV) is the causative agent of chicken pox and shingles. The overall objective of thisproposal is to understand the nature of physical and functional interactions between the complex VZV majortransactivator, IE62, and specific components of the cellular transcription apparatus. Such information is criticalto our understanding of the complex pathogenesis of VZV infection. It is particularly important in terms of thelive attenuated VZV vaccine. Vaccination is now recommended for all children and recently the FDA approvedthe vaccine for use in the elderly for the prevention of zoster based on an extensive clinical trial. Currently littleis known concerning attenuation of the vaccine virus. Since the IE62 gene accumulates the majority ofmutations in the attenuated vaccine strains, understanding its interaction with host functions could lead to thedevelopment of second generation vaccine whose molecular mechanism of attenuation is well understood.The work proposed involves three Specific Aims. Specific Aim 1: Functional Interaction of IE62 with CellularFactors. We will examine the functional interaction between the IE62 protein and two essential cellulartranscription factors the Mediator complex and HCF-1. This will be done by mapping and mutation ofinteracting domains and expression of these mutations in the context of the viral genome. Specific Aim 2: Roleof DNA Binding in the Mechanism of IE62 Activation. We will determine the specificity and affinity of the IE62-DNA Interaction and the effect of mutations in the DNA-binding domain on IE62 DNA-binding andtransactivation and viral gene expression. Specific Aim 3: Interrelationship Between IE62 Structure andFunction. We will mutate the IE62 SEAC domains and assess there function in in vitro transcription assays.The growth properties of virus carrying mutations in these domains will be determined. We will determine if thetwo transcriptional activation domains present in the IE62 homodimer are both required for IE62 function andwhat functions they perform. These studies will help us to understand the ways in which this important viralprotein influences the functions of cells following infection. Since the live attenuated VZV vaccine will be usedto prevent chicken pox and shingles throughout the U.S. population it is important to understand how the virusinteracts with its human host. This work should also result in information that could be used in strategies todevelop better anti-viral drugs and vaccines.en_US
dc.titleSTRUCTURE/FUNCTION OF VARICELLA ZOSTER VIRUS DNA.en_US
dc.typeNIH Grant Awarden_US


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