艾滋病功能性治愈猕猴模型创建及其病毒潜伏机制研究

项目名称： 艾滋病功能性治愈猕猴模型创建及其病毒潜伏机制研究

项目编号： No.81471620

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 郑永唐

作者单位： 中国科学院昆明动物研究所

项目金额： 145万元

中文摘要： 高效抗逆转录病毒疗法(HAART)是目前临床上最行之有效的抗HIV/AIDS治疗方案，但不能根治艾滋病，其根本原因是无法清除潜伏于机体中的病毒库。近年发现在少数(5-15％)早期治疗的HIV/AIDS患者中，停药后数年内病毒都没有出现反弹，实现了功能性治愈，为艾滋病治愈带来一线曙光。在这些患者体内，病毒的潜伏状态及其维持机制尚不清楚。本项目拟在前期艾滋病灵长类动物模型研究和技术平台基础上：用SIVmac239病毒感染中国猕猴，在感染早期进行HAART治疗，建立艾滋病功能性治愈猕猴模型；确定其治疗时机和方案；研究模型猕猴体内潜伏病毒在血液、各主要组织和器官的数量、活性和变异特征；研究病毒变异、宿主限制因子、免疫活化、microRNA和中和抗体对病毒潜伏的影响；了解功能性治愈的病毒潜伏机制。本项目将有助于阐明功能性治愈的机制，为艾滋病治疗策略提供科学依据。

中文关键词： 艾滋病；功能性治愈；动物模型；SIV；病毒潜伏

英文摘要： Highly active antiretroviral therapy (HAART) is the best way to treat HIV/AIDS, it can decline plasma HIV viral load to an undetectable level. Unfortunately, it does not cure AIDS, because viruses always recover replication at any time if the antiviral therapy is interrupted. Now it is widely accepted that the existence of long-lived latent HIV reservoirs is the primary obstacle to clear the virus infection.Recently,a small proportion of HIV patients were identified as post-treatment controllers whose viremia remained controlled for several years after the interruption of prolonged HAART initiated during the primary infection,these patients reach to a function cure state and bring great hope to the expectation of AIDS cure. However, The underlying reason to control virus replication and maintain its latency is not revealed by now. Rhesus macaques infected with SIV can closely resemble human AIDS and have facilitated many important advances in understanding the biology of HIV latency in human. In this study, Chinese rhesus macaque model will used to study the function cure:1) A number of Chinese macaques will be infected SIVmac239 and iniated a early and stretched combined HAART, then the treatment will be ceased for a extended time and some portion of macaques which can control virus repliction were distinguished as functional cure macaques, and the therapeutics applied will be determined. 2) Compared with non funtional cure macaques, the latent state of the viruses of functional cure macaques, such as the viral reservoirs, viral diversity and infectious ability will be detected in peripheral blood during the full procedure and in the mainly possible tissues and organs after animals were sacrificed. 3) Some viroloy and immunology parameters of functional cure macaques, such as virus variation, microRNA, host restriction factors, immune activation, CD8+ cytotoxic lymphocyte and neutralizing antibody will be tested and evaluated their role in virus latency.4)The underlying mechanism to control persistent low levels of virus replication and maintain virus latency in functional cure macaques will be analysed and somewhat explained. This work will contributed some solid data and set a better possible direction to the clinical therapy of HIV/AIDS.

英文关键词： AIDS;Functional cure;Animal model;SIV;Virus latency