Viral Persistence and Pathogenesis

病毒的持久性和发病机制

• 批准号: 10618834
• 负责人: Neal A. DeLuca
• 金额: $ 29.57万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-07-01 至 2025-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10618834
• 关键词: Pathogenesis; Viral

Project Summary Viruses have evolved a vast array of mechanisms to avoid detection and/or elimination by host defenses and to establish persistent infections that not only ensures survival in the human population, but can also contribute to pathogenesis. While we have developed effective antiviral drugs and vaccines against some important viruses, the threat of viral diseases worldwide remains, largely due to antigenic drift and shift, drug resistant mutants, emerging infectious agents, and importantly persistent or latent infections. The complexity and diversity of persistence and pathogenesis mechanisms utilized by viruses pose major challenges to the development of effective vaccines and chemical or immune-based treatments of virus diseases. To address these complex problems, it is essential to understand the mechanisms underlying viral persistence and pathogenesis, at the molecular level. Thus, there continues to be an urgent need to train a new generation of independent investigators with the interdisciplinary experience and expertise to address the complex issues of viral persistence and pathogenesis. A goal of the training program has been, and will continue to be, the recruitment of undergraduates and recent Ph.D. graduates in related disciplines (biochemistry, biological sciences, cellular and molecular biology, etc) into advanced studies in mechanisms of viral persistence and pathogenesis. The training program brings together the expanding number of basic science faculty devoted to the study of viruses and translational research in the Department of Microbiology and Molecular Genetics, the Department of Pediatrics, the Cancer Virology Program, and the Center for Vaccine Research at the University of Pittsburgh School of Medicine, and the Graduate School of Public Health. The Viral Persistence and Pathogenesis (VPP) training program offers a unique opportunity for the coordinated interdisciplinary research training of predoctoral trainees within the structure of the Program in Microbiology and Immunology (PMI) and postdoctoral trainees within the laboratories of the VPP faculty, with additional training via specialized course offerings, dedicated research seminars, retreats, and participation in national scientific meetings. Importantly, the VPP program is unique in that it leverages concepts in persistence and pathogenesis from diverse viral systems with the goal of educating trainees of the diversity of mechanisms, but also enabling the utilization of common themes for their research. Support for 4 predoctoral and 2 postdoctoral trainees per year is requested. The VPP program remains committed to the need to increase diversity in trainees, to provide training in the responsible conduct of research, and to provide career guidance for trainees.

项目摘要 病毒已经进化出大量的机制来避免被宿主检测和/或消除 防御和建立持续的感染，不仅确保生存的人口，但可以 也有助于发病机制。虽然我们已经开发出有效的抗病毒药物和疫苗， 尽管病毒是重要的病毒，但全球病毒性疾病的威胁仍然存在，主要是由于抗原漂移和转移，药物 耐药突变体，新出现的感染因子，以及重要的持续性或潜伏性感染。的复杂性 病毒的持久性和致病机制的多样性对人类的免疫系统构成了重大挑战。 开发有效的疫苗和病毒性疾病的化学或免疫治疗。解决 对于这些复杂的问题，了解病毒持续存在的机制至关重要， 发病机制，在分子水平上。因此，仍然迫切需要培训新一代的 具有跨学科经验和专业知识的独立调查员，以解决复杂的问题， 病毒持久性和发病机制。培训计划的目标一直是并将继续是 招收本科生和博士生相关学科毕业生（生物化学，生物 科学，细胞和分子生物学等），深入研究病毒持久性的机制， 发病机制培训计划汇集了越来越多的基础科学教师， 微生物学和分子遗传学系的病毒和转化研究， 该大学儿科系、癌症病毒学项目和疫苗研究中心 匹兹堡医学院和公共卫生研究生院。病毒的持久性和 发病机制（VPP）培训计划为协调的跨学科研究提供了一个独特的机会 在微生物学和免疫学（PMI）计划的结构内培训博士前学员， VPP学院实验室内的博士后学员，通过专业课程进行额外培训 提供，专门的研究研讨会，务虚会，并参加国家科学会议。重要的是， VPP计划的独特之处在于它利用了不同病毒的持久性和发病机理的概念 系统，目标是教育受训者了解机制的多样性，但也使他们能够利用 共同的研究课题。每年为4名博士前和2名博士后培训生提供支持， 所请求VPP计划仍然致力于增加受训人员的多样性， 培训负责任的研究行为，并为学员提供职业指导。

项目成果

The Vibrio cholerae RND efflux systems impact virulence factor production and adaptive responses via periplasmic sensor proteins.

弧形霍乱RND外排系统通过周质传感器蛋白影响毒力因子的产生和适应性反应。

• DOI: 10.1371/journal.ppat.1006804
• 发表时间: 2018-01
• 期刊: PLoS pathogens
• 影响因子: 6.7
• 作者: Bina XR;Howard MF;Taylor-Mulneix DL;Ante VM;Kunkle DE;Bina JE
• 通讯作者: Bina JE

Enter at your own risk: how enteroviruses navigate the dangerous world of pattern recognition receptor signaling.

• DOI: 10.1016/j.cyto.2013.05.007
• 发表时间: 2013-09
• 期刊: CYTOKINE
• 影响因子: 3.8
• 作者: Harris, Katharine G.;Coyne, Carolyn B.
• 通讯作者: Coyne, Carolyn B.

Glycosaminoglycan binding by arboviruses: a cautionary tale.

• DOI: 10.1099/jgv.0.001726
• 发表时间: 2022-02-01
• 期刊: The Journal of general virology
• 作者: Alcorn, Maria D H;Klimstra, William B
• 通讯作者: Klimstra, William B

Interferon signaling drives epithelial metabolic reprogramming to promote secondary bacterial infection.

• DOI: 10.1371/journal.ppat.1011719
• 发表时间: 2023-11
• 期刊: PLoS pathogens
• 影响因子: 6.7

Emerging concepts in dengue pathogenesis: interplay between plasmablasts, platelets, and complement in triggering vasculopathy.

登革热发病机制的新概念：浆母细胞、血小板和补体之间的相互作用引发血管病变。

• DOI: 10.1615/critrevimmunol.2014010212
• 发表时间: 2014
• 期刊: Critical reviews in immunology
• 影响因子: 1.3
• 作者: Nascimento,EduardoJM;Hottz,EugenioD;Garcia-Bates,TatianaM;Bozza,Fernando;MarquesJr,ErnestoTA;Barratt-Boyes,SimonM
• 通讯作者: Barratt-Boyes,SimonM