LSUHSC COBRE: ROLE OF INNATE IMMUNITY IN YELLOW FEVER VIRUS PATHOGENESIS

LSUHSC COBRE：先天免疫在黄热病病毒发病机制中的作用

• 批准号: 7720565
• 负责人: KATHERINE D RYMAN
• 金额: $ 35.16万
• 依托单位: LOUISIANA STATE UNIV HSC SHREVEPORT
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-06-01 至 2009-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7720565
• 关键词: Affect; Africa; Alphavirus; Americas; Attenuated; Attenuated Live Virus Vaccine; Biological Warfare; Bioterrorism; Computer Retrieval of Information on Scientific Projects Database; Culicidae; Dendritic Cells; Dengue Virus; Disease; Eastern Equine Encephalitis Virus; Emerging Communicable Diseases; Europe; Flavivirus; Fright; Funding; Genome; Goals; Grant; Immune response; Immunity; Immunization; Infection; Institution; Life; Lymphoid Tissue; Molecular; Mutation; Natural Immunity; Pan Genus; Phenotype; Primary Cell Cultures; Research; Research Personnel; Resources; Role; Source; Testing; Time; United States National Institutes of Health; Vaccines; Viral Hemorrhagic Fevers; Viral Pathogenesis; Virulent; Virus; West Nile virus; Yellow fever virus; attenuation; chemokine; cytokine; design; immunogenicity; in vivo; macrophage; monocyte; virus host interaction; virus pathogenesis

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The highly-lethal, pan-systemic hemorrhagic fever caused by the mosquito-borne yellow fever virus (YFV) was one of the most feared diseases in Africa, Europe and the Americas until the live-attenuated 17D vaccine was developed in the 1930's. To derive the 17D vaccine strain, the natural wild-type Asibi isolate of YFV was empirically passaged 176 times on primary cultured cells. Although 17D is considered a prototypic live-attenuated virus vaccine, one of the greatest mysteries in the flavivirus field is the molecular mechanism that controls the attenuation and immunogenicity of this live-attenuated vaccine. Our long-term goals are to reveal which of the mutations accumulated in the 17D genome are attenuating in vivo and determine their effect(s) on viral pathogenesis, and to determine how the attenuated infection differentially affects early virus-host interactions, eliciting YFV-specific protective immune responses after immunization with 17D. We are testing the hypothesis that early viremic dissemination of the live-attenuated 17D vaccine strain is significantly impaired in comparison with the virulent parental Asibi virus as a result of a differential ability to replicate in dendritic cells, monocytes and/or macrophages and that the attenuated phenotype will correlate with induction of chemokine/cytokines appropriate for stimulation of adaptive immunity in regional lymphoid tissues. It is anticipated that our findings will facilitate the rational design of other live-attenuated virus vaccines, particularly against other pathogenic flaviviruses (e.g., West Nile and dengue viruses) and the closely-related alphaviruses (e.g., eastern equine encephalitis virus), most of which are agents of both emerging infectious disease and bioterrorism/biowarfare.

该副本是利用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此可以在其他清晰的条目中代表。列出的机构是 对于中心，这不一定是调查员的机构。 由蚊子传播的黄热病病毒（YFV）引起的高度致命的，泛系统的出血热是非洲，欧洲和美洲最令人恐惧的疾病之一，直到1930年代开发了现场直播的17D疫苗。 为了得出17d疫苗菌株，在原代培养细胞上，YFV的天然野生型ASIBI分离株经验传递了176次。 尽管17D被认为是一种原型的活识别病毒疫苗，但Flavivirus领域中最大的谜团之一是控制这种活体增长疫苗的衰减和免疫原性的分子机制。我们的长期目标是揭示17D基因组中积累的哪些突变正在体内衰减，并确定其对病毒发病机理的影响，并确定减毒感染如何差异地影响早期病毒 - 宿主相互作用，从而引起YFV特异性的保护性免疫反应17D。我们正在检验以下假设：与毒性的亲本菌病毒相比，生命诱导的17d疫苗菌株的早期病毒传播显着受损，这是由于在树突状细胞，单核细胞和/或巨噬细胞中复制的差异能力而导致的，并且与刺激性的刺激性刺激了化学/或刺激性的现象，使现象构成了诱导的现象，使现象构成了诱导的诱导型。淋巴组织。预计我们的发现将促进其他活体病毒疫苗的合理设计，特别是针对其他致病性黄素病毒（例如，西尼罗河和登革热病毒）和与密切相关的α病毒（例如，东部马胸炎病毒），其中大多数是e Embi Bi Bi Bi Bi Bi Bi Biorsim and emering sof sof sof inforialiss和emerious sof。