Methamphetamine and AIDS in a Non-Human Primate Model

非人类灵长类动物模型中的甲基苯丙胺和艾滋病

基本信息

批准号：
8652443
负责人：
ANIL KUMAR
金额：
$ 35.17万
依托单位：
UNIVERSITY OF MISSOURI KANSAS CITY
依托单位国家：
美国
项目类别：
财政年份：
2008
资助国家：
美国
起止时间：
2008-09-30 至 2016-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8652443
关键词：
AIDS Dementia Complex AIDS/HIV problem Acquired Immunodeficiency Syndrome Address Affect American Animals Blood Body Weight decreased Brain Chronic Communities Control Animal Control Groups Disease Progression Evolution Exposure to Foxes Gays Gut associated lymphoid tissue HIV Seropositivity HIV Seroprevalence HIV-1 Health Human Immune response Immune system Individual Infection Long-Term Effects Macaca Macaca mulatta Methamphetamine Modeling Monitor Mucosal Immune Responses Neuraxis Neuropathogenesis Pathogenesis Prevalence Research Design Role SIV Seroprevalences Subfamily lentivirinae System Testing Time Viral Viral Load result Virus Virus Diseases Virus Replication club drug male men men who have sex with men methamphetamine abuse methamphetamine exposure nervous system disorder neuropathology nonhuman primate research study sex simian human immunodeficiency virus virus host interaction

项目摘要

DESCRIPTION (provided by applicant): Club drugs are extensively used by young people with more popularity among gay community (men having sex with men; MSM). It has been established that HIV seroprevalence is higher among methamphetamine users and methamphetamine is known to contribute to HIV-associated dementia (HAD) among HIV-positive individuals. There are also indirect and suggestive indications available that methamphetamine affects the virus replication, prevalence and progression of disease. The prospect of testing proof-of-concept studies regarding the role of methamphetamine in HIV positive humans is untenable because of the variable incubation periods and long time required to address this important issue. Therefore a well-designed study in the macaque model of HIV/AIDS is greatly warranted that will help conclude the effect of methamphetamine abuse on lentivirus pathogenesis, neurological disorder and disease progression in relatively short time. We propose to address these issues in this application. The application proposes to (i) establish the SIV-SHIV/macaque model of chronic methamphetamine exposure and examine whether methamphetamine abuse accelerates the onset of AIDS in macaques, (ii) determine whether chronic methamphetamine exposure affects virus-specific cellular, humoral and mucosal immune responses in SIV- SHIV/macaque model of AIDS, (iii) determine whether METH and SHIV/SIV interaction causes enhanced neuropathological effects on the virus/host interaction in the brain and alterations in dopaminergic systems, and (iv) determine whether virus evolution is different in methamphetamine-exposed macaques compared to that in the control animals.

描述（由申请人提供）：俱乐部毒品是在同性恋社区中更受欢迎的年轻人广泛使用的（男人与男性发生性关系； MSM）。已经确定，甲基苯丙胺使用者中的HIV血清阳性率更高，据已知甲基苯丙胺在HIV阳性个体中有助于HIV相关的痴呆症（HAT）。也有间接和暗示性的指示甲基苯丙胺会影响病毒复制，患病率和进展。测试有关甲基苯丙胺在艾滋病毒阳性人类中作用的概念验证研究的前景是站不住脚的，因为解决了这一重要问题所需的可变孵化期和长时间所需的时间。因此，非常有必要在艾滋病毒/艾滋病的猕猴模型中进行精心设计的研究，这将有助于结论甲基苯丙胺滥用对慢病毒发病机理，神经系统疾病和疾病进展的影响。我们建议在本申请中解决这些问题。该申请建议（i）建立慢性甲基苯丙胺暴露的SIV-SHIV/猕猴模型，并检查甲基苯丙胺滥用是否会加速猕猴的艾滋病发作，（ii）确定慢性甲基苯丙胺暴露是否会影响病毒特异性细胞，幽闭性和粘膜免疫，（iii）在SIV-SHIV/猕猴模型中的响应，（III）确定甲基和SHIV/SIV相互作用会导致神经病理学对大脑病毒/宿主相互作用的影响是否增强，以及多巴胺能系统的改变，（iv）确定病毒进化是否是与对照动物相比，甲基苯丙胺暴露的猕猴不同。

项目成果

期刊论文数量（19）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Involvement of metabotropic glutamate receptor 5, AKT/PI3K signaling and NF-κB pathway in methamphetamine-mediated increase in IL-6 and IL-8 expression in astrocytes.

DOI：
10.1186/1742-2094-9-52
发表时间：
2012-03-15
期刊：
Journal of neuroinflammation
影响因子：
9.3
作者：
Shah A;Silverstein PS;Singh DP;Kumar A
通讯作者：
Kumar A

Methamphetamine augment HIV-1 Tat mediated memory deficits by altering the expression of synaptic proteins and neurotrophic factors.

DOI：
10.1016/j.bbi.2018.04.018
发表时间：
2018-07
期刊：
Brain, behavior, and immunity
影响因子：
0
作者：
Nookala AR;Schwartz DC;Chaudhari NS;Glazyrin A;Stephens EB;Berman NEJ;Kumar A
通讯作者：
Kumar A

Multiple Protein Kinases via Activation of Transcription Factors NF-κB, AP-1 and C/EBP-δ Regulate the IL-6/IL-8 Production by HIV-1 Vpr in Astrocytes.