Compartmentalized CSF viral escape and the CNS HIV reservoir

区室化脑脊液病毒逃逸和中枢神经系统艾滋病毒储存库

基本信息

批准号：
10014060
负责人：
RICHARD W. PRICE
金额：
$ 36.04万
依托单位：
UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
依托单位国家：
美国
项目类别：
财政年份：
2015
资助国家：
美国
起止时间：
2015-09-30 至 2021-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10014060
关键词：
AIDS dementia Antibodies Biological Assay Biological Markers Blood Blood specimen Brain CD4 Positive T Lymphocytes Cells Central Nervous System Infections Cerebrospinal Fluid Cessation of life Chronic Clinical Companions Detection Development Diagnosis Disease Progression Evolution Focal Infection Funding Genome HIV HIV Infections Hematogenous Herpes zoster disease India Indolent Infection Inflammation Inflammatory Injury Lead Liquid substance Measures Methods Molecular Virology Neuraxis Neurologic Neurology Outcome Pathogenesis Phenotype Phylogenetic Analysis Plasma Population Proteins RNA Research Project Grants Sampling Source Sweden Systemic disease Systemic infection Technology Time Tropism Variant Viral Virus antiretroviral therapy central nervous system injury comparison group deep sequencing design immune activation inflammatory milieu insight nervous system disorder new technology novel parent grant programs relating to nervous system

项目摘要

Abstract Cerebrospinal fluid (CSF) HIV escape refers to clinical settings in which the magnitude of central nervous system (CNS) HIV infection, reflected in the CSF HIV RNA concentration, is equal to or exceeds the HIV RNA concentration measured in blood during antiretroviral therapy (ART). Three types of CSF escape have been identified: Neurosymptomatic, in which there is clear clinical evidence of CNS injury, Asymptomatic without documented injury, and Secondary provoked by a non-HIV CNS infection. Each of these develops in a setting where ART exerts less effect on CNS than systemic HIV infection, thereby permitting detailed examination of a relatively ‘isolated’ CNS viral population. This Supplemental proposal extends our ongoing research project in two ways. Specific Aim S1 introduces two rare and invaluable sample sets for molecular virological analysis to define the origins of CSF HIV populations in Neurosymptomatic and Secondary CSF Escape. Specific Aim S2 supports use of novel technology to measure a large array of CSF and blood biomarkers to better characterize the inflammatory and neurological features of all three types of CSF escape. Overall, these Supplementary studies will advance our understanding of the exchange between systemic and CNS HIV infection, including the contributions to from a CNS HIV reservoir and ongoing seeding from the blood. This understanding will advance the clinical recognition, diagnosis and management of these unusual aspects of treated HIV, and provide broader insights into the origins, pathogenesis and treatment of CNS HIV infections.

抽象的脑脊液 (CSF) HIV 逃逸是指临床环境中中枢神经系统的程度系统（中枢神经系统） HIV 感染，反映在脑脊液 HIV RNA 浓度上，等于或超过 HIV RNA 抗逆转录病毒治疗 (ART) 期间测量的血液浓度分为三种类型的脑脊液逃逸。已确定：有神经症状，其中有明确的中枢神经系统损伤临床证据，无症状，无症状已记录的损伤，以及由非 HIV 中枢神经系统感染引起的继发性损伤，这些都是在特定环境中发生的。 ART 对中枢神经系统的影响小于全身性 HIV 感染，因此可以详细检查该补充提案扩展了我们正在进行的研究项目。具体目标 S1 引入了两个稀有且宝贵的分子病毒学分析样本集。在神经症状和次要 CSF 特定目标 S2 中定义 CSF HIV 群体的起源。支持使用新技术来测量大量脑脊液和血液生物标志物，以更好地表征总体而言，这些补充说明了所有三种类型脑脊液逃逸的炎症和神经学特征。研究将增进我们对全身性和中枢神经系统艾滋病毒感染之间的交流的理解，包括中枢神经系统艾滋病毒储存库和血液中持续传播的贡献对治疗后的艾滋病毒这些不寻常方面的临床识别、诊断和管理，以及为中枢神经系统艾滋病毒感染的起源、发病机制和治疗提供更广泛的见解。

项目成果

期刊论文数量（14）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

What can characterization of cerebrospinal fluid escape populations teach us about viral reservoirs in the central nervous system?

DOI：
10.1097/qad.0000000000002253
发表时间：
2019-12-01
期刊：
AIDS
影响因子：
3.8
作者：
Joseph, Sarah B.;Trunfio, Mattia;Price, Richard W.
通讯作者：
Price, Richard W.

Potential for early antiretroviral therapy to reduce central nervous system HIV-1 persistence.

早期抗逆转录病毒治疗有可能减少中枢神经系统 HIV-1 的持续存在。

DOI：
10.1097/qad.0000000000002326
发表时间：
2019
期刊：
AIDS (London, England)
影响因子：
0
作者：
Spudich,Serena;Peterson,Julia;Fuchs,Dietmar;Price,RichardW;Gisslen,Magnus
通讯作者：
Gisslen,Magnus

Plasma Concentration of the Neurofilament Light Protein (NFL) is a Biomarker of CNS Injury in HIV Infection: A Cross-Sectional Study.

DOI：
10.1016/j.ebiom.2015.11.036
发表时间：
2016-01
期刊：
EBioMedicine
影响因子：
11.1
作者：
Gisslén M;Price RW;Andreasson U;Norgren N;Nilsson S;Hagberg L;Fuchs D;Spudich S;Blennow K;Zetterberg H
通讯作者：
Zetterberg H

Cerebrospinal Fluid Concentrations of the Synaptic Marker Neurogranin in Neuro-HIV and Other Neurological Disorders.

神经艾滋病毒和其他神经系统疾病中突触标记物神经粒蛋白的脑脊液浓度。

DOI：
10.1007/s11904-019-00420-1
发表时间：
2019
期刊：
Current HIV/AIDS reports
影响因子：
4.6
作者：
Yilmaz,Aylin;Fuchs,Dietmar;Price,RichardW;Spudich,Serena;Blennow,Kaj;Zetterberg,Henrik;Gisslén,Magnus
通讯作者：
Gisslén,Magnus

Viral co-infection, autoimmunity, and CSF HIV antibody profiles in HIV central nervous system escape.

HIV 中枢神经系统逃逸中的病毒共感染、自身免疫和脑脊液 HIV 抗体谱。

DOI：
10.1016/j.jneuroim.2023.578141
发表时间：
2023
期刊：
Journal of neuroimmunology
影响因子：
3.3
作者：
Hawes,IA;Alvarenga,BD;Browne,W;Wapniarski,A;Dandekar,R;Bartley,CM;Sowa,GM;DeRisi,JL;Cinque,P;Dravid,AN;Pleasure,SJ;Gisslen,M;Price,RW;Wilson,MR
通讯作者：
Wilson,MR