INFECTIVITY OF HSIV-VIF CHIMERA IN PIGTAILED MACAQUES
HSIV-VIF 嵌合体在斑尾猕猴中的感染性
基本信息
- 批准号:8357599
- 负责人:
- 金额:$ 37.79万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2011
- 资助国家:美国
- 起止时间:2011-05-01 至 2012-04-30
- 项目状态:已结题
- 来源:
- 关键词:Animal ModelAnimalsBlood CellsChimera organismDiseaseEngineeringFamily suidaeFundingGrantHIV-1HumanInfectionIntegration Host FactorsMacacaMacaca mulattaMacaca nemestrinaMediatingMedicineNational Center for Research ResourcesPilot ProjectsPlasmaPrimatesPrincipal InvestigatorProtein IsoformsProteinsResearchResearch InfrastructureResistanceResourcesSIVSourceTailTestingUnited States National Institutes of HealthViralViral Load resultViremiaVirionViruscollegecostimprovedin vivoinsightparticlepreventvif Genes
项目摘要
This subproject is one of many research subprojects utilizing the resources
provided by a Center grant funded by NIH/NCRR. Primary support for the subproject
and the subproject's principal investigator may have been provided by other sources,
including other NIH sources. The Total Cost listed for the subproject likely
represents the estimated amount of Center infrastructure utilized by the subproject,
not direct funding provided by the NCRR grant to the subproject or subproject staff.
Currently, there is no animal model for HIV-1 infection and disease because the virus is highly specific for humans. Macaques are generally resistant to HIV-1, with the exception being pig-tailed macaques. Our lab showed that pig-tailed macaques are unable to express functional isoforms of TRIM5-alpha, which has been identified as a host factor that restricts the replication of HIV-1 in rhesus monkeys. Therefore, it is possible that HIV-1 will only need to overcome restriction by another host factor, APOBEC3G/F, to replicate successfully in pig-tailed macaques. To test this hypothesis, we collaborated with Dr. J. Kimata of Baylor College of Medicine, who engineered an HIV-1 clone that includes the vif gene of SIVmne, allowing it to counteract APOBEC3G/F-mediated restriction. This chimeric virus, Pt-tropic HIV-1, is 96% HIV-1 and 4% SIV. It replicates in stimulated pig-tailed macaque blood cells as efficiently as SIVmne. In this pilot study, we inoculated 2 pig-tailed macaques intravenously with HSIV-vif. Both animals became infected and seroconverted, with plasma viremia detectable 1 wk after infection and reaching a peak between 104-105 copies/ml at wk 2.. Plasma viral load persisted for 10 months after infection between 102-103 copies/ml, but remained at baseline (d102 copies/ml) thereafter. To gain further insight on factors required for robust infection in pig-tailed macaques, we identified two notable differences between the Pt-tropic HIV-1 and SIVmne (1) SIV Vif does not associate with Pt-tropic HIV-1 viral particles; (2) while Pt-tropic HIV-1 degrades both Pt APOBEC3G and APOBEC3F, it prevents their inclusion in virions to a lesser extent than pathogenic SIVmne. Thus, while SIV Vif is necessary for persistent infection by Pt-tropic HIV-1, improved expression and inhibition of APOBEC3 proteins may be required for robust viral replication in vivo.
这个子项目是利用这些资源的众多研究子项目之一
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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Shiu-Lok Hu其他文献
Shiu-Lok Hu的其他文献
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{{ truncateString('Shiu-Lok Hu', 18)}}的其他基金
VIRUS-LIKE PARTICLES WITH STABILIZED TRIMERIC ENVELOPE FOR PRIME BOOST IMMUNIZATION
具有稳定三聚体包膜的病毒样颗粒,用于初免加强免疫
- 批准号:
9530535 - 财政年份:2017
- 资助金额:
$ 37.79万 - 项目类别:
PROTECTIVE EFFICACY OF GLYCAN-MODIFIED ENV VACCINE
聚糖修饰的 ENV 疫苗的保护作用
- 批准号:
8357597 - 财政年份:2011
- 资助金额:
$ 37.79万 - 项目类别:
IMMUNOPATHOGENESIS OF CLADE C SHIV-1157IPD3N4 IN M NEMESTRINA
M Nemestrina 中 C 进化枝 SHIV-1157IPD3N4 的免疫发病机制
- 批准号:
8357596 - 财政年份:2011
- 资助金额:
$ 37.79万 - 项目类别:
COMBINED APPROACH TO BROADLY PROTECTIVE AIDS VACCINES: PROJECT 4
广泛保护性艾滋病疫苗的综合方法:项目 4
- 批准号:
8357598 - 财政年份:2011
- 资助金额:
$ 37.79万 - 项目类别:
INFECTIVITY OF HSIV-VIF CHIMERA IN NEWBORN PIGTAILED MACAQUES
HSIV-VIF 嵌合体在新生短尾猴中的感染性
- 批准号:
8357619 - 财政年份:2011
- 资助金额:
$ 37.79万 - 项目类别:
INTRARECTAL TITRATION OF SHIV 162P4 STOCK
SHIV 162P4 库存的直肠内滴定
- 批准号:
8357586 - 财政年份:2011
- 资助金额:
$ 37.79万 - 项目类别:
ORIGIN AND EVOLUTION OF HIV-1 DRUG RESISTANCE
HIV-1 耐药性的起源和演变
- 批准号:
8357636 - 财政年份:2011
- 资助金额:
$ 37.79万 - 项目类别:
INTRARECTAL TITRATION OF SHIV 162P4 STOCK
SHIV 162P4 库存的直肠内滴定
- 批准号:
8172740 - 财政年份:2010
- 资助金额:
$ 37.79万 - 项目类别:
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