艾滋病毒(HIV)和丙肝病毒(HCV)合并感染已成为全球重要的公共卫生问题。除了HIV感染免疫细胞或HCV侵犯肝脏外，两种病毒都具有损害中枢神经系统的能力。现已知HIV和/或HCV感染会对中枢神经系统造成直接或间接损伤，导致认知障碍、脑病等严重后果，但尚不清楚HIV或HCV 感染中枢神经系统的靶细胞以及它们造成神经元损害的机制。本项目将分离人胚胎脑组织中的原代小胶质细胞、星形胶质细胞和神经元细胞,揭示HIV或HCV感染和复制的靶细胞，研究HIV和/或HCV感染对这些细胞内天然免疫因子（Ⅰ型、Ⅲ型干扰素，干扰素刺激因子及微小RNA等）的抑制以及对炎性因子（TNF-α,IL-1β，IL-6等）和氧自由基（ROS、NOS）的诱导，并在细胞和分子水平阐明两种病毒以及病毒蛋白对神经元损伤的作用机制，为研发治疗HIV和/或HCV介导的中枢神经损伤的药物提供必要的科学依据。

HIV and HCV coinfection has become a global public health problem. Both viruses have the ability to affect central nervous system (CNS) although HIV mainly infects immune cells whereas HCV infects hepatocytes. It is known that HIV and/or HCV infection can cause direct or indirect damages to the CNS, leading to cognitive dysfunction and mental disorders. However, we know little about the target cells of HIV or HCV in the CNS and the mechanisms of neuronal damages by HIV and/or HCV. In the proposed studies, we will utilize primary microglial cells, astrocytes and neurons isolated from human embryonic brains to investigate the target cells of HIV or HCV infection. We will examine the inhibitory effects of HIV and/or HCV infection on the expression of innate immunity factors (type Ⅰ and Ⅲ interferons, interferon stimulated genes and microRNAs) in these cells. We will also determine the effect of HIV and/or HCV infection on the production of inflammatory cytokines (TNF-α, IL-1β and IL-6) and oxygen species (reactive oxygen species and nitric oxygen species). Furthermore, we will determine the underlying mechanisms of HIV and/or HCV- or viral protein-mediated neuronal injury at both molecular and cellular levels. These studies will provide scientific evidence for the development of treatment strategies for HIV and/or HCV-mediated CNS damage.