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.

该副本是利用资源的众多研究子项目之一 由NIH/NCRR资助的中心赠款提供。对该子弹的主要支持 而且，副投影的主要研究员可能是其他来源提供的 包括其他NIH来源。 列出的总费用可能 代表subproject使用的中心基础架构的估计量， NCRR赠款不直接向子弹或副本人员提供的直接资金。 我们先前报道了SHIV感染后的韧带猕猴中多个粘膜位点CD4+ T细胞的快速损失。 感染后2-3周，观察到CD4+ CCR5+ T细胞和CD28-CD95+效应记忆细胞的深刻耗竭，与SHIV1157IPD3N4的R5热 - 热疗法一致。超出急性感染急性期研究的三只动物中有两只显示出48周的持续血浆病毒血症，而其余的动物则控制了基线时的血浆病毒载量（102份副本P mL）。从感染后24周开始，在两种持续的病毒动物中开发了交叉脱和中和的抗体。然而，两种动物都形成了与猿猴艾滋病一致的临床体征，并被安乐死。与Drs合作。露丝·鲁普雷希特（Ruth Ruprecht）和查尔斯·伍德（Charles Wood），我们研究了被感染的猪尾猕猴中病毒序列的演变，与人类和恒河猕猴感染了带有相同信封基因的病毒。初步结果表明，在所有三种物种的病毒感染过程中，包膜基因中发生了类似的变化，这进一步支持了使用猕猴物种作为研究人类HIV感染的模型。