Role of CNS Opportunistic Infections in Subsequent Development of HIV Encephaliti

中枢神经系统机会性感染在艾滋病毒脑炎后续发展中的作用

• 批准号: 8304304
• 负责人: CARLOS A PARDO-VILLAMIZAR
• 金额: $ 32.15万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-08-01 至 2014-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8304304
• 关键词: AIDS Dementia Complex; Acquired Immunodeficiency Syndrome; Address; Africa; African; Anti-Retroviral Agents; Area; Asia; Asians; Autopsy; Brain; Cells; Central Nervous System Diseases; Chemokine (C-C Motif) Receptor 5; Collaborations; Country; Data; Dementia; Developing Countries; Development; Disease; Functional disorder; Goals; Guidelines; HIV; HIV encephalitis; HIV-1; Human; Human Resources; In Vitro; Incidence; India; Infection; Inflammatory Infiltrate; Institution; Lead; Magnetic Resonance Imaging; Magnetic Resonance Spectroscopy; Meningeal; Microglia; Molecular; Morbidity - disease rate; National Institute of Mental Health; National Institute of Neurological Disorders and Stroke; Nervous system structure; Neuroglia; Neurologic; Neurologic Manifestations; Neuronal Injury; Neurosciences; Opportunistic Infections; Outpatients; Pathogenesis; Patients; Pharmaceutical Preparations; Population; Psychological Transfer; Reporting; Research Personnel; Risk; Role; Source; Specimen; Staging; Survivors; Techniques; Technology Transfer; Tissues; Toxoplasmosis; Tuberculosis; Universities; Viral; Virus; Virus Diseases; Work; brain cell; brain tissue; chemokine receptor; macrophage; meetings; mild neurocognitive impairment; mortality; prevent; psychologic; residence; socioeconomics

HIV dementia has only rarely been reported from countries infected with clade C virus. Opportunistic infections of the nervous system, however, are a major cause of morbidity and mortality in these developing countries. For example, in India where there are nearly 5 million patients are infected with the virus, it was estimated that nearly 25% of patients have CNS manifestations, most of which are opportunistic infections. Since these infections are treatable, it is imperative to determine the long-term impact of these infections on the brain. Preliminary data shows that the inflammatory infiltrates associated with these infections have a large number of HIV infected macrophages. It remains unknown, however, if inflammatory infiltrates associated with the opportunistic infection may serve as a portal of entry for HIV and if the virus may then establish residence in the brain and then continue to evolve within the brain. The degree to which these strains may cause neuro-glial cell dysfunction remains unknown. Further it remains unknown if patients with meningeal infiltrates would be at similar risks as those with parenchymal infiltrates. A major limitation to studying these neuropathological consequences of HIV clade C virus infection is the lack of autopsy tissues from these countries. NIMHANS is a unique institution that has conducted autopsies on patients that have died of AIDS since 1990. To the best of our knowledge, this is the only source of well characterized brain tissue specimens from HIV infected patients in Asia and Africa. This represents an excellent opportunity to address questions about disease pathogenesis that could not have been done otherwise. We thus propose to, 1. To determine the extent of glial cell activation and neuronal injury in HIV infected patients with CNS toxoplasmosis or tuberculosis. 2. To identify and compare viral sequences from HIV infected cells in inflammatory infiltrates associated with CNS toxoplasmosis or tuberculosis. 3. To determine if brain derived sequences of env and tat in inflammatory infiltrates cause glial cell activation or neuronal injury in vitro. These goals will be accomplished through collaborative efforts between Johns Hopkins University and NIMHANS. An excellent working relationship has already been established between the two institutions over the last several years. We have also devised a plan for training and technology transfer for the NIMHANS investigators.

感染C分支病毒的国家很少报告艾滋病毒痴呆症。 然而，神经系统的机会性感染是发病的主要原因。 以及这些发展中国家的死亡率。例如，在印度，那里几乎有 有500万名患者感染了这种病毒，估计有近25%的患者 有中枢神经系统的表现，大多数是机会性感染。因为这些 感染是可以治疗的，必须确定这些感染的长期影响 脑部感染。初步数据显示，炎症渗入 与这些感染相关的有大量感染艾滋病毒的巨噬细胞。它 然而，尚不清楚是否与机会主义相关的炎性渗透 感染可以作为艾滋病毒的进入门户，如果病毒随后可以建立 驻留在大脑中，然后在大脑中继续进化。在多大程度上 这些菌株可能会导致神经胶质细胞功能障碍，目前尚不清楚。在更远的地方，它仍然 尚不清楚脑膜浸润性疾病的患者是否会面临与其他患者类似的风险 实质渗入。研究这些神经病理学的一个主要限制是 感染HIV分支C病毒的后果是缺乏来自这些组织的尸检组织 国家。NIMHANS是唯一一家对患者进行尸检的机构 自1990年以来都死于艾滋病。据我们所知，这是唯一的 亚洲和非洲艾滋病毒感染者的脑组织样本特征良好。 这是一个很好的机会来回答有关疾病发病机制的问题 要不是这样，就不可能做到这一点。因此，我们建议，1.确定程度 HIV感染中枢神经系统患者神经胶质细胞激活和神经元损伤的研究 弓形虫病或肺结核。2.鉴定和比较来自HIV的病毒序列 与中枢神经系统弓形虫病相关的炎性浸润物中的感染细胞 肺结核。3.确定炎症性疾病中脑源性env和Tat序列是否存在 在体外，浸润物会引起神经胶质细胞的激活或神经元损伤。这些目标将是 通过约翰·霍普金斯大学和 尼姆汉斯。双方已经建立了良好的工作关系 在过去的几年里有两个机构。我们还制定了培训和培训计划 NIMHANS调查人员的技术转让。

项目成果

Eccentric target sign in cerebral toxoplasmosis: neuropathological correlate to the imaging feature.

• DOI: 10.1002/jmri.22192
• 发表时间: 2010-06
• 期刊: JOURNAL OF MAGNETIC RESONANCE IMAGING
• 影响因子: 4.4
• 作者: Kumar, G. G. Sharath;Mahadevan, A.;Guruprasad, A. S.;Kovoor, Jerry M. E.;Satishchandra, P.;Nath, Avindra;Ranga, Udaykumar;Shankar, S. K.
• 通讯作者: Shankar, S. K.

Usefulness of stereotactic biopsy and neuroimaging in management of HIV-1 Clade C associated focal brain lesions with special focus on cerebral toxoplasmosis.

• DOI: 10.1016/j.clineuro.2012.10.012
• 发表时间: 2013-07
• 期刊: Clinical neurology and neurosurgery
• 影响因子: 1.9
• 作者: Shyam babu C;Satishchandra P;Mahadevan A;Pillai Shibu V;Ravishankar S;Sidappa N;Udaykumar R;Ravi V;Shankar SK
• 通讯作者: Shankar SK

Host response profile of human brain proteome in toxoplasma encephalitis co-infected with HIV.

• DOI: 10.1186/1559-0275-11-39
• 发表时间: 2014
• 期刊: Clinical proteomics
• 影响因子: 3.8
• 作者: Sahu A;Kumar S;Sreenivasamurthy SK;Selvan LD;Madugundu AK;Yelamanchi SD;Puttamallesh VN;Dey G;Anil AK;Srinivasan A;Mukherjee KK;Gowda H;Satishchandra P;Mahadevan A;Pandey A;Prasad TS;Shankar SK
• 通讯作者: Shankar SK

Proteomic Analysis of the Human Anterior Pituitary Gland.

• DOI: 10.1089/omi.2018.0160
• 发表时间: 2018-12
• 期刊: Omics : a journal of integrative biology
• 作者: S. Yelamanchi;Ankur Tyagi;Varshasnata Mohanty;P. Dutta;M. Korbonits;S. Chavan;Jayshree Advani;Anil K. Madugundu;Gourav Dey;K. Datta;M. Rajyalakshmi;Nandini A. Sahasrabuddhe;A. Chaturvedi;Amit Kumar;A. A. Das-A.;Dhiman Ghosh;Gajendra M Jogdand;Haritha H. Nair;K. Saini;M. Panchal;Mansi Ashwinsinh Sarvaiya;S. S. Mohanraj-S.;Nabonita Sengupta;Priti Saxena;P. A. Subramani;Pradeep Kumar;Rakhil Akkali;S. Reshma;R. Santhosh;S. Rastogi;Sudarshan Kumar;S. Ghosh;V. K. Irlapati;A. Srinivasan;B. Radotra;P. Mathur;G. W. Wong;P. Satishchandra;Aditi Chatterjee;H. Gowda;A. Bhansali;A. Pandey;S. Shankar;A. Mahadevan;T. Prasad

Progressive multifocal leukoencephalopathy (PML) associated with HIV Clade C--is not uncommon.

与 HIV C 型相关的进行性多灶性白质脑病 (PML) 并不罕见。

• DOI: 10.1007/s13365-013-0168-8
• 发表时间: 2013
• 期刊: Journal of neurovirology
• 影响因子: 3.2
• 作者: Netravathi,M;Mahadevan,Anita;Satishchandra,Parthasarathy;Shobha,N;Mailankody,Pooja;Kandavel,Thennarasu;Jitender,Saini;Anantaram,G;Nagarathna,S;Govekar,S;Ravikumar,BV;Ravi,V;Shankar,SK
• 通讯作者: Shankar,SK