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
• 负责人: Shiu-Lok Hu
• 金额: $ 37.79万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 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: https://reporter.nih.gov/project-details/8357596
• 关键词: Acute; Animals; CCR5 gene; CD28 gene; CD4 Positive T Lymphocytes; Cells; Clinical; Collaborations; Evolution; Family suidae; Funding; Genes; Grant; HIV Infections; Human; Infection; Macaca; Macaca mulatta; Macaca nemestrina; Memory; Modeling; National Center for Research Resources; Phase; Plasma; Primates; Principal Investigator; Reporting; Research; Research Infrastructure; Resources; Simian Acquired Immunodeficiency Syndrome; Source; T-Lymphocyte; TNFRSF6 gene; Tail; Tropism; United States National Institutes of Health; Viral; Viral Load result; Viremia; Virus; Virus Diseases; Wood material; cost; mucosal site; neutralizing antibody; simian human immunodeficiency virus

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. We previously reported the rapid and substantial loss of CD4+ T cells at multiple mucosal sites in pigtailed macaques following SHIV infection. By 2-3 wks post-infection, profound depletion of CD4+CCR5+ T cells cells and CD28-CD95+ effector memory cells were observed, consistent with the R5-tropism of SHIV1157ipd3N4. Two of the three animals that were studied beyond the acute phase of infection showed persistent plasma viremia for gt 48 wks, while the remaining one controlled its plasma viral load at baseline (102 copies p ml). Cross-clade neutralizing antibodies developed in both persistently viremic animals starting at 24 weeks after infection. However, both animals developed clinical signs consistent with simian AIDS and were euthanized. In collaboration with Drs. Ruth Ruprecht and Charles Wood, we studied the evolution of viral sequences in infected pig-tailed macaques as compared to human and rhesus macaques infected with viruses bearing the same envelope gene. Preliminary results indicated that similar changes occurred in the envelope gene during the course of viral infection in all three species, lending further support to the use of macaque species as model to study HIV infection in humans.

该子项目是利用资源的众多研究子项目之一 由 NIH/NCRR 资助的中心拨款提供。子项目的主要支持 并且子项目的主要研究者可能是由其他来源提供的， 包括其他 NIH 来源。 子项目可能列出的总成本 代表子项目使用的中心基础设施的估计数量， NCRR 赠款不直接向子项目或子项目工作人员提供资金。 我们之前报道过猪尾猕猴感染 SHIV 后多个粘膜部位 CD4+ T 细胞迅速大量损失。 感染后 2-3 周，观察到 CD4+CCR5+ T 细胞和 CD28-CD95+ 效应记忆细胞的深度消耗，与 SHIV1157ipd3N4 的 R5 向性一致。在感染急性期之后进行研究的三只动物中，有两只显示出持续血浆病毒血症长达 48 周，而剩下的一只则将其血浆病毒载量控制在基线（102 拷贝/毫升）。感染后 24 周开始，两只持续病毒血症的动物均出现跨进化枝中和抗体。然而，两只动物都出现了与猿猴艾滋病一致的临床症状，并被安乐死。与博士合作。 Ruth Ruprecht 和 Charles Wood，我们研究了受感染的猪尾猕猴中病毒序列的进化，并将其与感染带有相同包膜基因的病毒的人类和恒河猴进行比较。初步结果表明，在所有三个物种的病毒感染过程中，包膜基因都发生了类似的变化，这为使用猕猴物种作为研究人类艾滋病毒感染的模型提供了进一步的支持。