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Structural and biochemical insights into multiple functions of HSV-1 UL21 in viral life cycle

HSV-1 UL21 在病毒生命周期中多种功能的结构和生化见解

基本信息

批准号：
9052050
负责人：
Claire Metrick
金额：
$ 3.93万
依托单位：
TUFTS UNIVERSITY BOSTON
依托单位国家：
美国
项目类别：
财政年份：
2015
资助国家：
美国
起止时间：
2015-04-01 至 2017-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9052050
关键词：
Affinity Bacterial RNA Binding Biochemical Biological Assay Biological Process Blindness C-terminal Capsid Cell Nucleus Cells Collaborations Communities Complex Cytoplasm DNA Data Disease Dissection Encephalitis Escherichia coli Future Gene Expression Genetic Transcription Genital system Genome Genomics Goals Herpesviridae Herpesvirus 1 Human Human Herpesvirus 2 Infection Knowledge Length Life Life Cycle Stages Lipids Membrane Membrane Proteins Messenger RNA Methods Minor Modeling Molecular Models Mutagenesis N-terminal Nuclear Nuclear Envelope Nucleic Acid Binding Nucleic Acids Oral Pathway interactions Play Proteins Proteolysis Research Research Personnel Role Simplexvirus Structure System Testing Therapeutic Transcriptional Regulation United States Universities Vaccines Vesicle Viral Viral Genes Viral Proteins Virus Virus Replication Work base design in vitro activity insight latent infection molecular modeling novel novel therapeutic intervention pathogen prevent protein complex protein function public health relevance skin lesion virus envelope

项目摘要

DESCRIPTION (provided by applicant): Herpes Simplex Viruses Type 1 and 2 (HSV-1 and HSV-2) are extremely prevalent and infect most people in the United States. These viruses cause lifelong, latent infections and can cause diseases from minor skin lesions to encephalitis. Unfortunately, preventative and therapeutic treatment options are limited. Networks of tegument proteins between the HSV-1 genomic capsid and envelope are likely to regulate many steps of the infection mechanism. A major gap in the progression of herpesvirology is the fact that the multiple specific functions of tegument proteins are largely unknown. Characterizing the many functions of these proteins is crucial to a complete understanding of the viral lifecycle. This proposal focuses on capsid-associated tegument protein UL21 that acts in the cytoplasm to regulate budding but is also found in the nucleus during infection. The objective of this proposal is to identify the multiple functions of HSV-1 UL21. The central hypothesis of this proposal is that UL21 has novel and unexplored nuclear functions in HSV-1 related to its ability to bind nucleic acids and localize to the nuclear rim. The hypothesis will be examined in two Specific Aims: Aim 1 will assess the binding of UL21 to nucleic acids and membranes to describe the mechanisms by which UL21 may regulate gene expression and nuclear egress, respectively. Furthermore, direct transcriptional effects of UL21 on UL16, another viral tegument protein, will be assayed in E coli. In Aim 2, the crystal structure of UL21 and its C- terminal domain will be solved and inspected for potential functional regions by characterizing the protein surface and by searching for structural similarity in proteins of known function. This proposal is significant because it will elucidate important functions previously hidden in the poorly understood tegument layer and aid researchers in assembling a more complete model of the infection mechanism-a necessary step to design new therapeutic strategies.