A Rhesus Macaque Model of HIV and HBV co-infection

项目总结 艾滋病毒和乙肝病毒都被认为是全球主要的健康问题。艾滋病毒感染了全球3700万人， 而乙肝病毒感染了2.57亿人。由于高度相似的传播途径，艾滋病毒/乙肝病毒混合感染很常见， 估计有10%的艾滋病毒感染者也感染了乙肝病毒。除了他们相似的性行为和 经皮传播途径，艾滋病毒和乙肝病毒也有能力驱动慢性感染，肝脏 功能障碍、肝纤维化和免疫衰竭。由于这些原因，艾滋病毒和乙肝病毒的混合感染是 与较高的健康并发症，特别是肝纤维化和肝细胞癌相关 癌症(HCC)。 感染艾滋病毒的患者进展为慢性乙肝病毒感染的可能性高达6倍，且病毒水平较高 乙肝病毒血症。艾滋病毒/乙肝患者肝功能障碍和肝纤维化加重的机制 目前还不了解合并感染的人。已经提出了多种假设，但有能力 缺乏可靠的乙肝病毒感染模型阻碍了对这些假说的研究。因此，仍然迫切需要 建立新的、生理上相关的艾滋病毒/乙肝病毒混合感染模型，以研究两者之间的相互作用 病毒。 在这里，我们提出了第一个恒河猴乙肝病毒感染模型，并提出了一种迫切需要的， 生理相关的HIV/乙肝病毒共感染动物模型。我们相信我们新的恒河猴模型 乙肝病毒感染将处于乙肝病毒研究的前沿，并将在关键时刻变得可用，努力 现在转向了治疗艾滋病毒和乙肝病毒的策略。由于迫切需要易驯服的动物模型 对于艾滋病毒/乙肝病毒混合感染，我们认为这里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.