Methamphetamine and AIDS in a Non-Human Primate Model

描述（由申请人提供）：俱乐部毒品被年轻人广泛使用，在同性恋群体中更受欢迎（男男性行为者；MSM）。已经确定，甲基苯丙胺使用者的艾滋病毒血清阳性率较高，并且已知甲基苯丙胺会导致艾滋病毒阳性个体中的艾滋病毒相关痴呆（HAD）。也有间接和暗示性的迹象表明，甲基苯丙胺影响病毒的复制、流行和疾病的进展。就甲基苯丙胺在艾滋病毒阳性人体中的作用进行概念验证性研究的前景是站不下去的，因为潜伏期不同，而且解决这一重要问题需要很长时间。因此，在HIV/AIDS猕猴模型中进行精心设计的研究是非常必要的，这将有助于在相对较短的时间内得出甲基苯丙胺滥用对慢病毒发病机制、神经紊乱和疾病进展的影响。我们建议在本应用程序中解决这些问题。本申请拟(i)建立慢性甲基苯丙胺暴露SIV-SHIV/猕猴模型，研究甲基苯丙胺滥用是否会加速猕猴艾滋病发病；（ii）确定慢性甲基苯丙胺暴露是否会影响SIV-SHIV/猕猴艾滋病模型的病毒特异性细胞、体液和粘膜免疫反应。（iii）确定甲基安非他明和SHIV/SIV相互作用是否会对大脑中的病毒/宿主相互作用和多巴胺能系统的改变产生增强的神经病理学影响，以及（iv）确定暴露于甲基苯丙胺的猕猴的病毒进化是否与对照动物不同。公共卫生相关性：本申请旨在测试慢性甲基苯丙胺滥用对艾滋病毒/艾滋病非人灵长类动物模型病毒复制、神经发病机制和病毒特异性免疫反应的影响。由于没有关于滥用甲基苯丙胺影响的资料，拟议的研究是非常有必要的。

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. PUBLIC HEALTH RELEVANCE: This application proposes to test the effect of chronic methamphetamine abuse on virus replication, neuropathogenesis and virus-specific immune responses in non-human primate model of HIV/AIDS. The proposed studies are highly warranted because there is no information available regarding effect of methamphetamine abuse.