Molecular studies of the astrocyte reservoir of HIV-1 in the central nervous system

人类免疫缺陷病毒1型(HIV-1)导致艾滋病，迄今已感染澳大利亚约2万人和全球4000多万人。在10-20%的艾滋病患者中，艾滋病毒感染中枢神经系统并导致艾滋病毒相关性痴呆。尽管采用了高效抗逆转录病毒疗法，但澳大利亚的流行率仍在继续上升，研究表明，东南亚地区的发病率一直偏低。中枢神经系统感染对艾滋病患者的治疗有两个主要影响。首先，与艾滋病毒相关的痴呆症是40岁以下人群中导致痴呆症的最常见原因，患有痴呆症的年轻人人数的持续增加给社区的卫生资源带来了越来越大的压力。第二，旨在根除艾滋病患者感染艾滋病毒的战略迄今没有考虑到感染患者中枢神经系统中存在的重要和独特的病毒储存库。HIV-1感染大脑的机制尚不清楚。了解艾滋病毒进入、感染和复制大脑的机制，对于制定最初预防大脑感染的制度以及开发预防痴呆症的有针对性的药物治疗至关重要。我们的初步研究表明，HIV感染大脑涉及独特的HIV病毒和细胞机制，不同于在血液和其他器官观察到的机制。本研究试图阐明这种机制。这项研究将有助于更好地了解HIV-1如何进入大脑并导致痴呆症，这两者对于开发治疗HIV-1感染的新药都是必不可少的。

Human immunodeficiency virus type 1 (HIV-1) causes AIDS and, to date, has infected approximately 20 thousand people in Australia and more than 40 million worldwide. HIV infects the central nervous system and causes HIV associated dementia in 10-20% of patients with AIDS. Despite the introduction of highly active antiretroviral therapy the prevalence in Australia continues to rise and studies have shown that the incidence has been under represented in the South east Asian region. Infection of the CNS has two major implications for the treatment of AIDS patients. Firstly, HIV-associated dementia is the most common cause of dementia in people under 40 and this continuing increase in the number of young adults with dementia is placing increased pressure on health resources in the community. Secondly, strategies aimed at eradicating HIV infection from AIDS patients have thus far have failed to take into account the important and unique viral reservoir present in the CNS of an infected patient. The mechanisms involved in HIV-1infection of the brain remain unclear. Understanding the mechanisms by which HIV enters, infects and replicates the brain, are pivotal to the development of regimes to prevent infection of the brain in the first instance as well as development of targeted drug therapy to prevent dementia. Our preliminary studies have shown that HIV infection of the brain involves unique HIV virus and cellular mechanism distinct to those observed for the blood and other organs. This study seeks to clarify such mechanisms. This study will contribute to a greater understanding of how HIV-1 enters the brain and causes dementia, both of which are essential to the development of new drugs to treat HIV-1 infection.