A Rhesus Macaque Model of HIV and HBV co-infection

项目摘要 HIV和HBV都被认为是主要的全球健康问题。全世界有3700万人感染艾滋病毒， 而HBV感染了2.57亿人。由于传播途径高度相似，HIV/HBV合并感染很常见， 估计10%的HIV感染者也感染HBV。除了他们相似的性和 经皮传播途径，艾滋病毒和HBV也有能力驱动慢性感染，肝 功能障碍、肝纤维化和免疫衰竭。由于这些原因，合并感染HIV和HBV是 与更高的健康并发症的可能性相关，特别是肝纤维化和肝细胞癌 癌（HCC）。 HIV感染者进展为慢性HBV感染的可能性高达6倍， HBV病毒血症导致HIV/HBV患者肝功能障碍和纤维化增加的机制 目前尚不清楚合并感染的个体。已经提出了多种假设，但 研究这些假设的障碍是缺乏一个强大的HBV感染模型。因此，仍然迫切需要 开发新的、生理学相关的HIV/HBV合并感染模型，以研究它们之间的相互作用。 病毒 在这里，我们提出了第一个HBV感染的恒河猴模型，并提出了一个迫切需要的， 生理学相关的HIV/HBV共感染动物模型。我们相信我们新的恒河猴模型 HBV感染将成为HBV研究的前沿，并在关键时刻变得可用， 现在正转向治疗HIV和HBV的策略。考虑到对易于驾驭的动物模型的迫切需求 HIV/HBV合并感染的研究，我们认为本文提出的研究具有最高的意义。

PROJECT SUMMARY HIV and HBV are both recognized as major global health concerns. HIV infects 37 million people worldwide, while HBV infects 257 million. HIV/HBV co-infection is common due to highly similar routes of transmission, with an estimated 10% of HIV-infected individuals also infected with HBV. In addition to their similar sexual and percutaneous routes of transmission, HIV and HBV also share the ability to drive chronic infection, liver dysfunction, liver fibrosis, and immune exhaustion. For these reasons, co-infection with HIV and HBV is associated with higher probabilities of health complications, particularly liver fibrosis and hepatocellular carcinoma (HCC). HIV infected patients are up to 6-times more likely to progress to chronic HBV infection and have higher levels of HBV viremia. The mechanisms contributing to the increased liver dysfunction and fibrosis seen in HIV/HBV co-infected individuals are not currently understood. Multiple hypotheses have been proposed, but the ability to study these hypotheses is hindered by lack of a robust HBV infection model. Thus, there remains an urgent need to develop novel, physiologically relevant models of HIV/HBV co-infection to study the interaction between these viruses. Here, we present the first rhesus macaque model of HBV infection and propose an urgently needed, physiologically relevant HIV/HBV co-infection animal model. We believe that our new rhesus macaque model of HBV infection will be on the forefront of HBV research, and is becoming available at a crucial time where efforts are now turning towards cure strategies for both HIV and HBV. Given the urgent need for tractable animal models of HIV/HBV co-infection, we believe the research proposed herein to be of the highest significance.