Monitoring SIV Reservoirs with Whole Body immunoPET

使用全身免疫 PET 监测 SIV 储库

基本信息

批准号：
9087144
负责人：
PHILIP J SANTANGELO
金额：
$ 104.32万
依托单位：
UNIVERSITY OF LOUISIANA AT LAFAYETTE
依托单位国家：
美国
项目类别：
财政年份：
2014
资助国家：
美国
起止时间：
2014-07-15 至 2019-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9087144
关键词：
Accounting Acquired Immunodeficiency Syndrome Acute Address Affect Affinity Anatomy Animal Model Anti-Retroviral Agents Antiviral Agents Biomedical Engineering Biopsy Blood CD4 Positive T Lymphocytes Cell Lineage Cells Clinic Clinical Couples Therapy Detection Development Disease Progression Drug Kinetics Exposure to Foundations Goals HIV HIV Infections Health Heating Human Image Imaging Techniques Immune In Situ In Vitro Individual Infection Infection prevention Interruption Kinetics Label Life Lymphoid Tissue Macaca Macaca mulatta Maps Measures Metabolism Methods Modeling Monitor Monkeys Monoclonal Antibodies Nature Organ Outcome Pathology Patients Pattern Pharmaceutical Preparations Pharmacodynamics Plasma Positron-Emission Tomography Preventive measure Primates Process Protocols documentation Radionuclide Imaging Regimen Residual state Route SIV Sampling Signal Transduction Site Staging Technetium Tc 99m ciprofloxacin Techniques Testing Time Tissue Banks Universities Vaccines Vagina Variant Viral Viral Load result Viral Proteins Viral reservoir Virus Virus Diseases Virus Replication X-Ray Computed Tomography antiretroviral therapy base body map clinical application design imaging modality immune activation improved in vivo innovation nonhuman primate novel novel strategies rectal therapeutic vaccine tool transmission process viral RNA viral detection virus pathogenesis

项目摘要

DESCRIPTION (provided by applicant): With the advent of novel anti-retroviral therapies, the prospect of potentially eliminating HIV from infected patients may become an achievable goal. However, such goal will require new tools with greater sensitivity than currently available to monitor the progress of such therapy, no only in blood but also in organs that do harbor such reservoirs and sites of residual viral replication in vivo. In addition, identifying early seeding of viral reservoirs during acute infecton relative to the route of transmission and disease progression may open novel directions for chemotherapeutic or immune barriers to contain the new virus infection foyers and generalized dissemination of the infection with seeding of viral reservoirs. To harness such early viral dynamics and account for the natural individual variation that exists for such dynamics, there is a need to understand the dissemination patterns of HIV infection following mucosal transmission, the primary transmission mode of infection worldwide. However, the tools currently available to monitor such viral processes are either indirect or relatively invasive and clearly impractical for the human clinic. Even when one uses the nonhuman primate model of AIDS, understanding the viral dynamics in real time is challenging and prohibitively expensive if one chooses to perform serial sacrifices, not to mention fraught by a high degree of variability between individuals. In this project, we propose to optimize our established immuno-positron emission tomography (PET) with simultaneous X-ray computed tomography (CT), to determine real-time whole body maps of simian immunodeficiency virus replication sites in vivo to chart out the total body replication sites of SIV in vivo and determine viral dynamics and sites of residual viral replication during antiretroviral therapy. Thus we propose to determine the anatomic SIV viral dynamics following infection via the IV, rectal and vaginal route to determine the consecutive major sites of viral replication in vivo, which will be confirmed via targeted tissue collections. Next we will compare 2 combination ART therapies for reducing viral reservoirs and document residual foyers of replication in vivo as well as determine which such reservoirs might be fueling the viral resurgence after interruption of ART in vivo. We submit that these studies wil provide critical information for the design of HIV eradication strategies in human HIV infection.

描述（由申请人提供）：随着新型抗逆转录病毒疗法的出现，从感染患者体内消除艾滋病毒的前景可能成为一个可以实现的目标。然而，这一目标将需要比目前可用的灵敏度更高的新工具来监测这种治疗的进展，不仅在血液中，而且在体内确实存在此类病毒储存库和残留病毒复制位点的器官中。此外，识别急性感染过程中相对于传播途径和疾病进展的病毒储存库的早期播种可能会为化疗或免疫屏障开辟新的方向，以遏制新的病毒感染场所，并通过病毒储存库的播种来广泛传播感染。为了利用这种早期病毒动态并解释这种动态存在的自然个体差异，有必要了解粘膜传播（全球感染的主要传播模式）后艾滋病毒感染的传播模式。然而，目前可用于监测此类病毒过程的工具要么是间接的，要么是相对侵入性的，并且对于人类临床来说显然不切实际。即使使用艾滋病的非人类灵长类动物模型，如果选择进行连续牺牲，实时了解病毒动态也是具有挑战性的，而且成本高昂，更不用说个体之间存在高度的变异性。在这个项目中，我们建议优化我们已建立的免疫正电子发射断层扫描（PET）和同步X射线计算机断层扫描（CT），以确定猿猴免疫缺陷病毒体内复制位点的实时全身图，从而绘制出总复制位点。体内 SIV 的体内复制位点，并确定抗逆转录病毒治疗期间的病毒动态和残留病毒复制位点。因此，我们建议确定通过静脉、直肠和阴道途径感染后的解剖学 SIV 病毒动力学，以确定体内病毒复制的连续主要位点，这将通过目标组织收集来证实。接下来，我们将比较两种减少病毒储存库的组合 ART 疗法，并记录体内复制的残留门厅，并确定哪些此类储存库可能会在体内 ART 中断后助长病毒的复活。我们认为这些研究将为设计人类艾滋病毒感染的艾滋病毒根除策略提供关键信息。