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Inflammation associated with HIV infection: role of receptor cross-talk

与 HIV 感染相关的炎症：受体串扰的作用

基本信息

批准号：
10016292
负责人：
Yuri Persidsky
金额：
$ 64.52万
依托单位：
TEMPLE UNIV OF THE COMMONWEALTH
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-09-30 至 2024-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10016292
关键词：
Ache Acquired Immunodeficiency Syndrome Acute Address Agonist Analgesics Animals Attenuated Axonal Neuropathy Bilateral Blood - brain barrier anatomy Brain Bromides CCL2 gene CCL3 gene CCL4 gene CCR1 gene CCR5 gene Cells Chemotaxis Chronic Development Disease Enkephalins Epidemic Event Exposure to Failure Fiber Foundations Generations Genetic HIV HIV Envelope Protein gp120 HIV Infections Headache Highly Active Antiretroviral Therapy In Vitro Individual Infection Inflammation Inflammatory Inflammatory Response Intravenous Intravenous Drug Abuse Ligands Link Morbidity - disease rate Morphine Mouse Strains Mus Neurologic Neuropathy Opioid Opioid Analgesics Opioid Antagonist Opioid Receptor Opioid abuser Organ Pain Pain management Pathologic Patients Phosphorylation Play Population Process Production Proteins Receptor Activation Receptor Cross-Talk Recurrent pain Reporting Role Signal Pathway Stimulus Syndrome Testing Transgenic Mice antiretroviral therapy base chemokine chemokine receptor chronic pain clinically significant cytokine desensitization drug abuser humanized mouse in vivo morphine administration mortality mouse model mu opioid receptors neuroinflammation novel opiate tolerance opioid abuse pain sensitivity painful neuropathy release of sequestered calcium ion into cytoplasm response

项目摘要

Abstract: Opiate drug abuse is a critical contributor to the global AIDS epidemic, and over a third of HIV infections in the U.S. can be linked to intravenous drug abuse. Recent estimates suggest that almost 20% of intravenous drug abusers are infected with HIV. HIV-associated neuropathy remains a clinically significant issue for patients infected with HIV, even in the current era of anti-retroviral therapy. In addition, HIV-infected opiate abusers demonstrate a more severe neuropathy than non-opiate abusers, and the basis for the greater neuropathy remains uncertain. In this application, we propose that HIV infection in the brain results in an inflammatory response, which promotes the production of inflammatory chemokines, leading to the activation of the respective chemokine receptors, resulting in the cross-desensitization of opioid receptors. The consequence of this set of events is an elevated sensitivity to pain stimuli. We propose to test these processes using mouse models to evaluate the influence of HIV gp120 in the induction of neuroinflammation, including the associated neuropathic pain. Our proposed studies will also attempt to address the ability of morphine to attenuate the development of this pain response. We also propose to confirm these studies through the analysis of an authentic HIV infection using a humanized mouse model. We believe the results from these studies will greatly enhance our understanding of the mechanisms which contribute to the development of neuroinflammation in HIV-infected subjects, including those who are opiate abusers.

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