IMMUNE CONTROL OF WEST NILE VIRUS QUASISPECIES DYNAMICS

西尼罗河病毒准种动态的免疫控制

• 批准号: 9207426
• 负责人: James D Brien
• 金额: $ 10.8万
• 依托单位: SAINT LOUIS UNIVERSITY
• 依托单位国家: 美国
• 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/9207426
• 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; Flavivirus; Future; Generations; Genes; Genetic; Genetic Variation; Genomics; Goals; Growth; HIV; HIV/HCV; Hepatitis C; IFNAR1 gene; IRF1 gene; IRF3 gene; Immune; Immune response; Immunocompetence; In Vitro; Individual; Infection; Innate Immune Response; Innate Immune System; Interferon Receptor; Interferon Type I; Interferon-alpha; Interferons; Lead; Lipids; Mediating; Modeling; Monitor; Mouse Strains; Mus; Mutation; Nature; Nucleotides; Organ; Pathogenesis; Pathology; Pathway interactions; Phenotype; 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 immune response; autocrine; cell type; deep sequencing; design; effective therapy; experimental study; gene function; immunogenicity; in vivo; mRNA Transcript Degradation; macrophage; member; novel strategies; paracrine; pressure; response; tool; transmission process; viral fitness; virus genetics

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（由申请方提供）：RNA病毒在自然界中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，称为病毒群或准种。这个建议的目的是表征病毒序列变异的功能性后果的主机内，不同的免疫能力使用西尼罗河病毒作为一个模型。该建议旨在确定I型干扰素反应如何区别地限制病毒生长，这是由遗传同质性与异质性病毒群体引起的疾病。它还解决了I型IFN对WNV基因组进化的影响，从而更好地理解受I型IFN信号传导途径限制的病毒序列和多样性（核苷酸和蛋白质）。更深入地了解I型IFN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IFN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，因为大多数疫苗来自感染性克隆，这是同源病毒的来源。

项目成果

Prior Heterologous Flavivirus Exposure Results in Reduced Pathogenesis in a Mouse Model of Zika Virus Infection.

• DOI: 10.1128/jvi.00573-21
• 发表时间: 2021-07-26
• 期刊: Journal of virology
• 影响因子: 5.4
• 作者: Hassert M;Steffen TL;Scroggins S;Coleman AK;Shacham E;Brien JD;Pinto AK
• 通讯作者: Pinto AK

Diagnostic differentiation of Zika and dengue virus exposure by analyzing T cell receptor sequences from peripheral blood of infected HLA-A2 transgenic mice.

• DOI: 10.1371/journal.pntd.0008896
• 发表时间: 2020-12
• 期刊: PLoS neglected tropical diseases
• 影响因子: 3.8
• 作者: Hassert M;Wolf KJ;Rajeh A;Schiebout C;Hoft SG;Ahn TH;DiPaolo RJ;Brien JD;Pinto AK
• 通讯作者: Pinto AK

CD4+T cells mediate protection against Zika associated severe disease in a mouse model of infection.

• DOI: 10.1371/journal.ppat.1007237
• 发表时间: 2018-09
• 期刊: PLoS pathogens
• 影响因子: 6.7
• 作者: Hassert M;Wolf KJ;Schwetye KE;DiPaolo RJ;Brien JD;Pinto AK
• 通讯作者: Pinto AK