IMMUNE CONTROL OF WEST NILE VIRUS QUASISPECIES DYNAMICS

西尼罗河病毒准种动态的免疫控制

基本信息

批准号：
8635271
负责人：
James D Brien
金额：
$ 16.07万
依托单位：
SAINT LOUIS UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2016
资助国家：
美国
起止时间：
2016-02-01 至 2018-01-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8635271
关键词：
Address Amalgam Antibodies Antiviral Agents Attenuated Live Virus Vaccine Brain C57BL/6 Mouse Cells Congenic Mice Data Dendritic Cells Dengue Virus Development Disease Escape Mutant Evolution Family member Fibroblasts Flaviviridae Future Generations Genes Genetic Genetic Variation Genomics Goals Growth HIV Hepatitis C virus IFNAR1 gene IRF1 gene IRF3 gene Immune Immune response Immune system Immunocompetence In Vitro Individual Infection Interferon Type I Interferons Lead Lipids Mediating Modeling Monitor Mouse Strains Mus Mutation Nature Nucleotides Organ Pathogenesis Pathology Pathway interactions Population Proteins RNA Viruses RNA-Directed RNA Polymerase Resistance Retroviridae Role Safety Serial Passage Serum Severity of illness Signal Pathway Signal Transduction Sorting - Cell Movement Source Spleen Translations Vaccines Variant Viral Viral Genome Virulence Virus Virus Diseases West Nile virus Work adaptive immunity autocrine cell type deep sequencing design effective therapy gene function immunogenicity in vivo mRNA Transcript Degradation macrophage member novel strategies paracrine pressure research study response tool transmission process type I interferon receptor viral fitness virus genetics

项目摘要

DESCRIPTION (provided by applicant): RNA viruses do not exist in nature as a single genomic sequence, but rather as an amalgam of related sequences referred to as a viral swarm or quasispecies. This proposal is designed to characterize the functional consequences of virus sequence variation within hosts that vary in immunological competence using WNV as a model. This proposal aims to identify how the type I IFN response differentially restricts viral growth an disease caused by a genetically homogenous versus heterogeneous virus population. It also addresses the effect of type I IFN on the evolution of the WNV genome, leading to a better understanding of the viral sequences and diversity (both nucleotide and protein) that are restricted by the type I IFN signaling pathway. A greater understanding of the interactions between type I IFN and a viral swarm could promote novel strategies to limit viral diversity, immune escape, and disease severity. In addition, understanding how type I IFN controls viral evolution could promote increased safety and immunogenicity of live attenuated vaccines, as most vaccines are derived from infectious clones, a source of homogenous virus.

描述（由申请人提供）：RNA病毒在自然界中并不作为单一基因组序列存在，而是作为相关序列的混合物存在，被称为病毒群或准种。该提案旨在以西尼罗河病毒为模型，描述免疫能力不同的宿主内病毒序列变异的功能后果。该提案旨在确定 I 型 IFN 反应如何差异性地限制病毒生长（一种由遗传同质病毒群与异质病毒群引起的疾病）。它还解决了 I 型 IFN 对 WNV 基因组进化的影响，从而更好地了解受 I 型 IFN 信号通路限制的病毒序列和多样性（核苷酸和蛋白质）。更好地了解 I 型干扰素和病毒群之间的相互作用可以促进限制病毒多样性、免疫逃逸和疾病严重程度的新策略。此外，了解 I 型干扰素如何控制病毒进化可以提高减毒活疫苗的安全性和免疫原性，因为大多数疫苗都源自感染性克隆，即同质病毒的来源。