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

• 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
• 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

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.

摘要 脑脊髓液（CSF）HIV逃逸是指中枢神经系统疾病的严重程度 系统（CNS）HIV感染，反映在CSF HIV RNA浓度中，等于或超过HIV RNA浓度 在抗逆转录病毒治疗（ART）期间在血液中测量的浓度。三种类型的脑脊液逃逸已经 确定：神经症状性，其中有明确的CNS损伤临床证据，无症状性， 记录的损伤，以及由非HIV CNS感染引起的继发性。每一个都是在一个环境中发展起来的 其中ART对CNS的影响小于系统性HIV感染，从而允许详细检查 相对“孤立”的CNS病毒群。这一补充建议扩展了我们正在进行的研究项目， 两种方式。Specific Aim S1为分子病毒学分析引入了两种罕见且宝贵的样品集， 定义神经症状性和继发性CSF逃逸中CSF HIV人群的起源。具体目标S2 支持使用新技术测量大量CSF和血液生物标志物，以更好地表征 所有三种类型的CSF逃逸的炎症和神经学特征。总的来说，这些补充 研究将促进我们对系统性和中枢神经系统HIV感染之间交换的理解，包括 从中枢神经系统艾滋病病毒库和持续的播种从血液的贡献。这种理解将 促进对艾滋病毒治疗后这些不寻常方面的临床识别、诊断和管理， 为CNS HIV感染的起源、发病机制和治疗提供了更广泛的见解。

项目成果

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)
• 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

Compartmentalization of cerebrospinal fluid inflammation across the spectrum of untreated HIV-1 infection, central nervous system injury and viral suppression.

• DOI: 10.1371/journal.pone.0250987
• 发表时间: 2021
• 期刊: PloS one
• 影响因子: 3.7
• 作者: Gisslen M;Keating SM;Spudich S;Arechiga V;Stephenson S;Zetterberg H;Di Germanio C;Blennow K;Fuchs D;Hagberg L;Norris PJ;Peterson J;Shacklett BL;Yiannoutsos CT;Price RW
• 通讯作者: Price RW