新发人持续性G病毒II型复制和感染细胞培养模型的建立及与HCV/HIV共感染的机制研究

人持续性G病毒II型(HPgV-2)是2015年新发现的黄病毒科病毒，尚无可进行基因操作的病毒感染性克隆和复制子以及细胞培养模型，限制了对其生命周期及复制机制的研究。HPgV-2是单股正链RNA病毒，基因组高度保守，但核心抗原不完整，提示HPgV-2可能是复制缺陷性病毒。我们的研究发现，HPgV-2与丙型肝炎病毒(HCV)，特别是HCV和人免疫缺陷病毒(HIV-1)共感染密切相关。因此，我们推测HPgV-2的复制可能需要HCV辅助，HIV-1可促进HCV复制而利于HPgV-2建立感染。为研究HPgV-2的复制机制并检验我们的假设，本项目将构建HPgV-2全长cDNA克隆和复制子，筛选合适细胞株，建立细胞培养模型，探讨HPgV-2复制以及和HCV/HIV-1共感染的机制。为深入研究HPgV-2的致病性、病毒与宿主相互作用以及多病毒共感染的机制等提供必需的研究平台，具有重要的科学意义。

Human pegivirus type II (HPgV-2), a positive strand RNA virus, was identified in hepatitis C patients in 2015. At present, there is no cell culture model for HPgV-2. Its association with human diseases and its replication mechanism remain to be elucidated. Our preliminary results indicate that HPgV-2 infection is tightly associated with hepatitis C virus (HCV), in particular HCV and human immunodeficiency virus (HIV) co-infection. Furthermore, HPgV-2 does not contain an intact core protein, which suggests that it may be a defect virus. Therefore, we propose that HPgV-2 needs the help of HCV for its efficient replication through HCV core protein trans-complementation. HIV can enhance HCV replication, which in turn supports the establishment of HPgV-2 infection. The goal of this study is to develop HPgV-2 permissive cell culture models by constructing HPgV-2 molecular infectious clone and screening appropriate cells to establish efficient replication cell system for HPgV-2. The cell culture model will be used to investigate HPgV-2 replication, to elucidate the role of HCV and HIV in HPgV-2 replication, and is of great importance and significance.