LONGITUDINAL FOLLOW UP OF SIVMAC PATHOGENESIS IN MACAQUES OF CHINESE ORIGIN

中国猕猴 SIVMAC 发病机制的纵向追踪

• 批准号: 7562259
• 负责人: Binhua Julie Ling
• 金额: $ 7.16万
• 依托单位: TULANE UNIVERSITY OF LOUISIANA
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-05-01 至 2008-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7562259
• 关键词: Acquired Immunodeficiency Syndrome; Acute; Alleles; Animals; CCR5 gene; CD8B1 gene; Cells; Chinese People; Chronic Phase; Computer Retrieval of Information on Scientific Projects Database; Disease Progression; Flow Cytometry; Funding; Genetic; Grant; Gut associated lymphoid tissue; Haplotypes; Immunogenetics; Infection; Institution; Journals; MHC Class I Genes; Macaca; Macaca mulatta; Measures; Memory; Monkeys; Paper; Pathogenesis; Plasma; Publishing; Recovery; Research; Research Personnel; Resources; SIV; Source; T-Lymphocyte; Testing; United States National Institutes of Health; Universities; Viral; Viral Load result; Wisconsin; day; follow-up; in vivo; restoration; virology

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. We have tested the dynamics of memory CD4+CCR5+ cells (target cells) in GALT in 12 SIV infected Chinese-origin rhesus macaques. Expression of T cell, naive and memory markers were measured by flow cytometry. Eight of 12 monkeys developed AIDS between 6 to 25 months after infection (progressors); 4 were long term nonprogressors (LTNPs) and remained healthy with undetectable plasma viral loads. Memory CD4+ CCR5+ cells were profoundly depleted during acute infection in all 12 monkeys. In progressors, all lacked the ability to maintain restoration of target cells. In the LTNPs, variable memory cell recovery began at day 60 PI and all had restored ¿ 15% of baseline levels by day 180 and maintained this level or increased it. In vivo CD8+ depletion in 2 LNTPs resulted in one to develop AIDS (V542) and the other (AJ07) remains healthy. Our results indicated that profound depletion of target cells in GALT was indistinguishable between progressors and LTNPs in the acute infection. Restoration of target cells during the chronic phase predicted LTNP. Sufficient CD8+ T cells are essential for controlling SIV infection in GALT and required for restoration of target cells. Moreover, host genetic protective factors such as immunogenetics was further studied by analyzing MHC class I alleles, more than 10 new MHC class I locus A and locus B alleles were identified from 9 Chinese-origin rhesus macaques with 48-190 clones per animal. However, when compared progressors with LTNPs, no association of disease progression was found with any particular MHC class I alleles. One recently published paper also indicated that control of simian immunodeficiency virus SIVmac239 is not predicted by inheritance of Mamu-B*17-containing haplotypes by David O'connor's group in the University of Wisconsin (Journal of Virology 2007406-410). Mamu-B*17 was previously recognized as an allele that associated with viral suppression and slow progression.

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