NeuroVirology & Biology Core

项目摘要/摘要：神经病毒学和生物学(NVB) 神经病毒学和生物学(NVB)的核心将专注于神经艾滋病毒的四个主要主题，与 HIV神经行为研究中心(HNRC)的优先事项和OAR科学议程：1)病毒的影响 HIV在中枢神经系统(CNS)持续存在的表观遗传学，2)潜伏或临床无症状的共同 感染，3)线粒体生物发生，4)脑巨噬细胞和星形胶质细胞对全身炎症介质的反应 炎症和当前的抗逆转录病毒治疗(ART)。NVB核心将继续增强HNRC的 通过与神经行为和精神病学、神经医学、 微生物组和发育核心，并利用特定于中枢神经系统的实验室和分析技术 病毒和细胞群体在神经认知和其他神经行为后果的背景下。 NVB的核心由两个互补的单位组成：神经病毒学单位和神经生物学单位。这些单位 将是HNRC不可或缺的一部分，并将提供宝贵的知识和技术 提高研究效率和科学投入，以实现中心的总体目标和目标。 ·神经病毒学股将提供专业知识和广泛的经验证和临床相关的 最高质量和最方便的实验室化验。这个单位有一项研究 将重点放在中枢神经系统内艾滋病毒的持久性上，并将继续提供检测，以确定艾滋病毒宿主的特征 在大脑和髓系细胞中，新的重点是前病毒表观遗传学。它将提供尖端的测序 方法从临床标本中刻画HIV前病毒的表观遗传格局。该单位将 描述病毒(遗传型和表型)和其他因素(混合感染、炎症、线粒体 损害)与神经认知和其他神经行为后果有关，如抑郁。 ·神经生物学股将对人类进行最先进的神经生物学和神经病理学分析 脑组织和体外实验系统，使神经艾滋病毒研究人员了解细胞 情绪和神经认知障碍的相关机制。它将分析潜在的神经毒性 当前ART方案对特定神经胶质细胞群的影响。神经生物学部门将调查 ART和HIV对大脑线粒体生物发生的影响，以及在体外暴露于ART的培养。在……里面 支持该中心扩大对抑郁症和抑郁症相关因素的关注，该股将研究 抗抑郁药物对神经元动态平衡的影响，着重于自噬和 相关的看门人，例如大脑免疫亲和素。神经生物学股将纳入生物标记物 使用CNTN/NNTC的库标本，研究计划中来自神经医学核心的发现。 最后，NVB核心将继续提供优质服务，实施改进的战略规划流程， 扩大其计划收入体系，保持确定所提供服务的灵活性，并扩大广泛的 已向艾滋病毒调查人员提供的服务数量。

PROJECT SUMMARY/ABSTRACT: NeuroVirology and Biology (NVB) The NeuroVirology and Biology (NVB) core will focus on four major themes underlying NeuroHIV, in line with the HIV Neurobehavioral Research Center (HNRC) priorities and the OAR scientific agenda: 1) the impact of viral epigenetics on HIV persistence in the central nervous system (CNS), 2) latent or clinically asymptomatic co- infections, 3) mitochondrial biogenesis, 4) brain macrophage and astroglial response to systemic mediators of inflammation and current antiretroviral therapy (ART). The NVB core will continue to enhance the HNRC’s transdisciplinary focus through close collaborations with the NeuroBehavioral and Psychiatry, NeuroMedical, Microbiome and Developmental Cores, and utilizing laboratory and analytic techniques specific to CNS-derived viral and cellular populations in the setting of neurocognitive and other neurobehavioral consequences. The NVB Core is structured in two complementary units: NeuroVirology Unit and NeuroBiology Unit. These units will be an integral and indispensable part of the HNRC, and will provide invaluable knowledge and technologies to enhance research productivity and scientific input to meet the Center’s overall goals and objectives. · The NeuroVirology Unit will provide expertise and a broad range of validated and clinically relevant laboratory-based assays with the highest quality and most convenience possible. This Unit has a research focus on HIV persistence within the CNS and will continue to offer assays to characterize the HIV reservoir in the brain and in myeloid cells, with a new focus on proviral epigenetics. It will offer cutting-edge sequencing methods to characterize the epigenetic landscape of the HIV provirus from clinical samples. This Unit will characterize viral (genotypic and phenotypic), and other factors (co-infections, inflammation, mitochondrial damage) associated with neurocognitive and other neurobehavioral consequences, such as depression. · The NeuroBiology Unit will perform state-of-the-art neurobiology and neuropathology analyses of human brain tissues and in vitro experimental systems, that allow NeuroHIV investigators to understand the cellular mechanisms associated with mood and neurocognitive disorders. It will analyze the potential neurotoxic effects of current ART regimens on specific neuroglial cell populations. The NeuroBiology Unit will investigate the effect of ART and HIV on mitochondrial biogenesis in brains, and in vitro in cultures exposed to ART. In support of the Center’s expanded focus on depression and depression related factors, this unit will study the impact of anti-depressant medication on neuronal homeostasis, focusing on markers of autophagy and associated gatekeepers, e.g. brain immunophilins. The NeuroBiology Unit will incorporate the biomarker findings from the NeuroMedical Core in the research plans using banked specimens from the CNTN/NNTC. Finally, the NVB core will continue to provide quality service, implement improved strategic planning processes, expand its program income system, maintain flexibility to determine offered services, and expand the extensive number of services already available to HIV investigators.