Host and viral determinants of hepatitis C virus macaque infection
丙型肝炎病毒猕猴感染的宿主和病毒决定因素
基本信息
- 批准号:9012008
- 负责人:
- 金额:$ 26.36万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2015
- 资助国家:美国
- 起止时间:2015-02-10 至 2017-01-31
- 项目状态:已结题
- 来源:
- 关键词:Animal ModelAnimal Testing AlternativesAnimalsCD81 geneCell Culture TechniquesCellsChimera organismDefectDetectionDevelopmentDiseaseEnzymesEthicsExhibitsFigs - dietaryGeneticGenotypeGoalsGrantHCV Animal ModelsHIV-1HealthHepaticHepatitis CHepatitis C AntibodiesHepatitis C VaccineHepatitis C virusHepatocyteHumanImmunityImmunocompetentInfectionInflammationLeadLeftLiverLiver diseasesMacacaMacaca mulattaMacaca nemestrinaMalignant neoplasm of liverModelingMonitorMonkeysMusMutationNorth AmericaPan GenusPathogenesisPatientsPlayPrimary carcinoma of the liver cellsPrimatesProcessProteinsReagentResearchResearch PersonnelRiskRoleSamplingSerumStructural GenesSupporting CellTestingTimeTropismUnited StatesUnited States National Institutes of HealthVaccine DesignVaccinesVariantViralVirusVirus ReceptorsVirus ReplicationWorkarmbaseclinically relevantcombatfitnessin vivoinduced pluripotent stem cellinsightliver injurymutantpathogenresearch studyscreeningtoolvaccine evaluationviral RNAvirus geneticsvirus pathogenesis
项目摘要
DESCRIPTION (provided by applicant): The hepatitis C virus (HCV) is the leading cause of liver cancer in the Western Hemisphere. Over 170 million people are infected with this virus and consequently at increased risk of liver damage and cancer. Understanding how this virus induces liver disease and the development of a much-needed vaccine requires an immunocompetent HCV animal model. The dogma in the HCV field was that this virus only infects humans and chimpanzees. As a recent NIH moratorium on chimpanzee research has effectively prohibited use of these animals, an alternative immunocompetent HCV animal model is desperately needed. To explore if small primates can support HCV infection, we generated hepatocytes from pigtail macaque-(Macaca nemestrina, Mn) induced pluripotent stem cell-derived hepatic cells. Surprisingly, these cells supported detectable levels of infection with cell
culture derive genotype 2a HCV. We found that inefficient function of the macaque version of the HCV receptor, CD81, limited HCV infection of these cells. A mutant genotype 2a virus that can use CD81 proteins from a wide range of species overcame this block and efficiently infected the macaque hepatocytes. We have recently made the startling discovery that both wild type and mutant versions of this virus could infect pigtail macaques in vivo, thus demonstrating for the first time that HCV can replicate in animals other than humans and chimpanzees. In this grant we propose experiments to further characterize macaque HCV infections. This will include determining if rhesus macaques, which are more readily available and a larger set of species-specific reagents than pigtail macaques are obtainable, can also be infected with genotype 2a HCV. We will also examine the viral determinants for HCV infection of macaques. We will explore mechanisms by which virus can adapt to more efficiently replicate in this host and determine if we are able to expand the range of viral isolates that can infect NHPs. Ultimately, our studies will provide the first immunocompetent tractable animal models that will establish new avenues to explore HCV replication and pathogenesis in vivo with the eventual goal of developing efficacious vaccine against this virus.
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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Matthew J Evans其他文献
Enforcing Metal-Arene Interactions in Bulky p-Terphenyl Bis(anilide) Complexes of Group 2 Metals (Be-Ba): Potential Precursors for Low-Oxidation-State Alkaline Earth Metal Systems.
强化第 2 族金属 (Be-Ba) 的大体积对三联苯双(苯胺)配合物中的金属-芳烃相互作用:低氧化态碱土金属体系的潜在前体。
- DOI:
- 发表时间:
2024 - 期刊:
- 影响因子:4.6
- 作者:
Dat T Nguyen;Christoph Helling;Matthew J Evans;Cameron Jones - 通讯作者:
Cameron Jones
N-Heterocyclic Germylenes Supported by Bulky Dianionic N,N-Chelating Ligands
大体积双阴离子 N,N-螯合配体支持的 N-杂环甲锗烷基
- DOI:
10.1016/j.jorganchem.2024.123143 - 发表时间:
2024 - 期刊:
- 影响因子:2.3
- 作者:
Dat T Nguyen;Matthew J Evans;Cameron Jones - 通讯作者:
Cameron Jones
Matthew J Evans的其他文献
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{{ truncateString('Matthew J Evans', 18)}}的其他基金
Zika virus nonstructural protein 5 inhibition of interferon signaling
寨卡病毒非结构蛋白 5 对干扰素信号传导的抑制
- 批准号:
10641222 - 财政年份:2023
- 资助金额:
$ 26.36万 - 项目类别:
Deep mutational scanning of the Zika virus NS5 protein
寨卡病毒 NS5 蛋白的深度突变扫描
- 批准号:
10171769 - 财政年份:2020
- 资助金额:
$ 26.36万 - 项目类别:
Deep mutational scanning of the Zika virus NS5 protein
寨卡病毒 NS5 蛋白的深度突变扫描
- 批准号:
10057677 - 财政年份:2020
- 资助金额:
$ 26.36万 - 项目类别:
Host and viral determinants of hepatitis C virus macaque infection
丙型肝炎病毒猕猴感染的宿主和病毒决定因素
- 批准号:
8914166 - 财政年份:2015
- 资助金额:
$ 26.36万 - 项目类别:
Hepatitis C virus polarized cell entry pathways
丙型肝炎病毒极化细胞进入途径
- 批准号:
8523846 - 财政年份:2012
- 资助金额:
$ 26.36万 - 项目类别:
Hepatitis C virus polarized cell entry pathways
丙型肝炎病毒极化细胞进入途径
- 批准号:
8396182 - 财政年份:2012
- 资助金额:
$ 26.36万 - 项目类别:
Occludin-specific HCV cell entry mechanisms
Occludin 特异性 HCV 细胞进入机制
- 批准号:
8337067 - 财政年份:2011
- 资助金额:
$ 26.36万 - 项目类别:
Studies of hepatitis C virus polarized cell entry and host factor requirements
丙型肝炎病毒极化细胞进入和宿主因子要求的研究
- 批准号:
7448969 - 财政年份:2008
- 资助金额:
$ 26.36万 - 项目类别:
Studies of hepatitis C virus polarized cell entry and host factor requirements
丙型肝炎病毒极化细胞进入和宿主因子要求的研究
- 批准号:
7707255 - 财政年份:2008
- 资助金额:
$ 26.36万 - 项目类别: