权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Structural Studies of Human Papillomavirus

人乳头瘤病毒的结构研究

基本信息

批准号：
10448451
负责人：
Susan Hafenstein
金额：
$ 75.15万
依托单位：
PENNSYLVANIA STATE UNIV HERSHEY MED CTR
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-08-13 至 2023-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10448451
关键词：
Address Affect Affinity Antibodies Antibody Response Anus Basal Cell Binding Capsid Capsid Proteins Cells Cervical Characteristics Collaborations Communities Computers Cryoelectron Microscopy Epitopes Genome Head Cancer Head and Neck Cancer Healthcare Human Human Papilloma Virus Vaccine Human Papillomavirus Human papilloma virus infection Human papillomavirus 16 Immune Immune response Immunologics Infection Knowledge L2 viral capsid protein Life Cycle Stages Link Location Malignant - descriptor Malignant Neoplasms Malignant neoplasm of cervix uteri Maps Minor Molecular Molecular Biology Molecular Conformation Monoclonal Antibodies Neck Cancer Patients Persons Pharmaceutical Preparations Process Production Proteins Public Health Research Research Personnel Resolution Scheme Shapes Structural Protein Structure System Techniques Throat Cancer Time Vaccine Design Vaccines Virus Virus-like particle aged design effective therapy improved men non-smoking novel therapeutics particle pathogenic virus receptor response stoichiometry three dimensional structure vaccine development

项目摘要

Project Summary/Abstract Human papillomaviruses (HPVs) are cancer-causing viruses. More than 250,000 people die each year from these cancers, particularly cervical, anal, and head and neck (H&N) cancers. Immune proteins known as antibodies can protect against these viruses and successful vaccines must induce such antibodies. Current vaccines can protect us against only two of the 15 HPV types found in cervical and H&N cancers. Better and more lasting control of HPV infections requires improved knowledge of how these antibodies protect and which are the “best” antibodies to provide this protection. Our studies are focused at understanding the exact interactions between HPV capsids and human cells during an infection. We will use cryo-electron microscopy (cryo-EM) and computer-driven high resolution techniques to define these interactions at atomic resolution, starting with a better more detailed examination of the capsids. For decades researchers have relied on the use of various virus like particles (VLPs) that are now known to have different characteristics, especially in the regions that illicit a host immune response. Part of this characterization is to map the location and incorporation of the minor structural protein (L2) that has important function during entry and is conserved across species. Understanding L2 function will reveal a significant target that has remained uncharacterized until now and may allow researchers to redirect the immune antibody response towards a more effective and long-lasting protective HPV vaccine. Finally, we are engaged in understanding the mechanisms that drive entry of HPV. We have begun to understand how the virus changes shape during entry into human cells. Targeting the conformational changing virus is an important new direction for creating new drugs to stop infection.

项目总结/文摘