Structural Studies of Human Papillomavirus

人乳头瘤病毒的结构研究

基本信息

批准号：
10238166
负责人：
Susan Hafenstein
金额：
$ 76.35万
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 2025-07-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10238166
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 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.

项目概要/摘要人乳头瘤病毒 (HPV) 是一种致癌病毒，每年有超过 25 万人死于该病毒。这些癌症，特别是宫颈癌、肛门癌和头颈癌 (H&N)，称为免疫蛋白。抗体可以预防这些病毒，成功的疫苗必须诱导这种抗体。疫苗只能保护我们免受宫颈癌和 H&N 癌症中发现的 15 种 HPV 类型中的两种的侵害。更持久地控制 HPV 感染需要更好地了解这些抗体如何保护以及哪些是提供这种保护的“最佳”抗体。我们的研究重点是了解 HPV 衣壳和人体细胞之间的确切相互作用我们将使用冷冻电子显微镜 (cryo-EM) 和计算机驱动的高分辨率技术来检测感染。从对衣壳进行更好、更详细的检查开始，以原子分辨率定义这些相互作用。几十年来，研究人员一直依赖于使用各种病毒样颗粒（VLP），现在已知这些颗粒具有不同的特征，特别是在引起宿主免疫反应的区域。是绘制在过程中具有重要功能的次要结构蛋白 (L2) 的位置和掺入图了解 L2 功能将揭示一个重要的目标。迄今为止仍未得到表征，可能允许研究人员重新定向免疫抗体反应最后，我们致力于了解一种更有效、更持久的保护性 HPV 疫苗。驱动 HPV 进入的机制我们已经开始了解病毒在进入过程中如何改变形状。靶向构象变化的病毒是创造新病毒的重要新方向。药物来阻止感染。