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.

这个子项目是许多利用资源的研究子项目之一 由NIH/NCRR资助的中心拨款提供。子项目的主要支持 而子项目的主要调查员可能是由其他来源提供的， 包括其它NIH来源。 列出的子项目总成本可能 代表子项目使用的中心基础设施的估计数量， 而不是由NCRR赠款提供给子项目或子项目工作人员的直接资金。 我们以前报道过，在猪流感病毒感染后，短尾猕猴的多个粘膜部位的CD 4 + T细胞迅速而大量丢失。 在感染后2-3周，观察到CD 4 + CCR 5 + T细胞和CD 28-CD 95+效应记忆细胞的深度消耗，这与SHIV 1157 ipd 3 N4的R5向性一致。在感染急性期后研究的三只动物中，有两只表现出持续的血浆病毒血症，持续时间为gt 48周，而剩下的一只在基线时控制了其血浆病毒载量（102拷贝/ml）。从感染后24周开始，在两种持续性病毒血症动物中均产生了交叉进化枝中和抗体。然而，这两只动物都出现了与猿类艾滋病一致的临床体征，并被安乐死。在与Ruth Ruprecht和Charles Wood博士的合作中，我们研究了感染猪尾猕猴的病毒序列的演变，并与感染携带相同包膜基因的病毒的人类和恒河猴进行了比较。初步结果表明，在所有三个物种的病毒感染过程中，包膜基因发生了类似的变化，进一步支持使用猕猴物种作为模型来研究人类的HIV感染。