Studies of Natural SIV Infection of Sooty Mangabeys

乌白白眉自然SIV感染的研究

• 批准号: 7535176
• 负责人: Guido Silvestri
• 金额: $ 108.43万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-12-15 至 2010-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7535176
• 关键词: Acquired Immunodeficiency Syndrome; African; Alveolar; Animal Housing; Animal Model; Animals; Apoptotic; Asians; Biopsy; Bone Marrow; Bromodeoxyuridine; CCR5 gene; CD4 Positive T Lymphocytes; CD8B1 gene; Cell Count; Cell Death; Cells; Cercocebus atys; Color; Comparative Study; Death Rate; Development; Disease; Disease Outcome; Disease Progression; Disease Resistance; Epidemic; Event; Exhibits; HIV; HIV Infections; HIV-2; Homeostasis; Human; Immune; Immune system; Individual; Infection; Irrigation; Label; Life; Longevity; Lymphocyte; Lymphoid Tissue; Macaca mulatta; Measures; Memory; Modeling; Monkeys; Mucous Membrane; Natural regeneration; Outcome; Pathogenesis; Phase; Predisposition; Primates; Production; Research; Research Personnel; SIV; Sampling; Site; Subfamily lentivirinae; Surveys; T-Cell Activation; T-Cell Depletion; T-Lymphocyte; Testing; Thymus Gland; Time; Translating; Universities; Viral; Viremia; Virus; Virus Replication; Work; antiretroviral therapy; base; comparative; cytokine; design; effective therapy; improved; in vivo; insight; lymph nodes; mucosal site; novel; programs; receptor; rectal; research study; transmission process

DESCRIPTION (provided by applicant): In contrast to HIV-infected individuals, sooty mangabeys (SMs), an African monkey species that is a natural host for SIV, live an apparently normal lifespan in captivity despite many years of SIV infection. Although SMs are typically infected with a highly replicating virus, only a subset (10-15%) display moderate to severe CD4+ T cell depletion and, in fact, the development of an AIDS-like illness is very rare. The aim of this project is to understand how SIV-infected SMs maintain CD4+ T cell homeostasis and avoid progression to AIDS. We will perform comparative studies of SIV-infected SMs with normal and depleted CD4+ T cell compartments. Pathogenic SIV infection of rhesus macaques (RMs), a non-natural host Asian monkey species, will also be used as a comparative model. The proposed studies will test three fundamental hypotheses that may explain why SIV infection of SMs is significantly less pathogenic than HIV infection of humans and SIV infection of RMs: (i) the average lifespan of virus infected cells is longer (and/or the fraction of virus produced by long-lived cells is higher); (ii) the infection is associated with lower levels of T cell turnover; and (iii) the virus infects a more limited subset of CD4+ T cells. The results of these studies will improve our understanding of the mechanisms underlying the lack of disease in SIV-infected SMs. These conceptual advances may provide insights for the pathogenesis of HIV infection in humans and may translate into the design of more effective treatments for AIDS.

描述（由申请人提供）：与 HIV 感染者相比，乌白眉猴（SM）是一种非洲猴类，是 SIV 的天然宿主，尽管感染了多年的 SIV，但在圈养条件下，其寿命明显正常。尽管 SM 通常感染高度复制的病毒，但只有一小部分 (10-15%) 表现出中度至重度 CD4+ T 细胞耗竭，事实上，发展为类似 AIDS 疾病的情况非常罕见。该项目的目的是了解感染 SIV 的 SM 如何维持 CD4+ T 细胞稳态并避免进展为 AIDS。我们将对感染 SIV 的 SM 与正常和耗尽的 CD4+ T 细胞区室进行比较研究。恒河猴 (RM)（一种非自然宿主亚洲猴种）的致病性 SIV 感染也将用作比较模型。拟议的研究将测试三个基本假设，这些假设可以解释为什么 SM 的 SIV 感染的致病性明显低于人类的 HIV 感染和 RM 的 SIV 感染：(i) 病毒感染细胞的平均寿命更长（和/或长寿细胞产生的病毒更高）； (ii) 感染与 T 细胞更新水平较低有关； (iii) 病毒感染更有限的 CD4+ T 细胞亚群。这些研究的结果将提高我们对 SIV 感染的 SM 缺乏疾病的机制的理解。这些概念上的进步可能为人类艾滋病毒感染的发病机制提供见解，并可能转化为更有效的艾滋病治疗方法的设计。