A Rhesus Macaque Model of HIV and HBV co-infection

HIV和HBV混合感染的恒河猴模型

基本信息

批准号：
10559577
负责人：
Benjamin J Burwitz
金额：
$ 76.3万
依托单位：
OREGON HEALTH & SCIENCE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-03-20 至 2026-02-28
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10559577
关键词：
Acceleration Adenoviruses Adolescent Adult Africa South of the Sahara Animal Model Animals Blood CD8-Positive T-Lymphocytes Cause of Death Cells Chronic Chronic Hepatitis B Circular DNA Clinical Codon Nucleotides DNA Ducks Ensure Frequencies Genome Genomics HBV Genotype HBV Liver Disease HIV HIV Infections Health Hepatitis B Acquisition Hepatitis B Infection Hepatitis B Virus Hepatocyte Human Immune Immunosuppression Individual Infection Intravenous Liver Liver Dysfunction Liver Fibrosis Liver diseases Macaca Macaca mulatta Modeling Monitor Mus Pan Genus Pathogenesis Patients Persons Physiological Positioning Attribute Prealbumin Prevalence Primary carcinoma of the liver cells Primates Probability Regimen Research Route SIV Sampling Serotyping Serum Southeastern Asia Structure Surface Antigens T cell response T-Lymphocyte Taurine Cholate Techniques Testing Time Tissues Transgenic Organisms Transplantation Viral Load result Viral Vector Viremia Virion Virus Woodchuck Work acute infection chronic infection co-infection cohort constriction design effector T cell exhaustion experience gene therapy genetic manipulation global health high risk in vivo liver biopsy nonhuman primate novel polypeptide prevent promoter receptor transmission process vector

项目摘要

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.

项目概要 HIV 和 HBV 均被认为是全球主要健康问题。艾滋病毒感染了全世界 3700 万人，而乙型肝炎病毒感染人数为 2.57 亿。由于传播途径高度相似，HIV/HBV 混合感染很常见，据估计，10% 的 HIV 感染者也感染了 HBV。除了他们相似的性和通过经皮传播途径，HIV 和 HBV 也具有共同的驱动慢性感染、肝功能障碍、肝纤维化和免疫衰竭。由于这些原因，HIV 和 HBV 合并感染是与较高的健康并发症可能性相关，特别是肝纤维化和肝细胞性肝病癌（HCC）。 HIV 感染患者进展为慢性 HBV 感染的可能性高达 6 倍，且水平更高乙型肝炎病毒血症。 HIV/HBV 肝功能障碍和纤维化增加的机制目前尚不清楚共同感染者的情况。已经提出了多种假设，但有能力由于缺乏稳健的乙型肝炎病毒感染模型，这些假设的研究受到阻碍。因此，仍然迫切需要开发新的、生理相关的 HIV/HBV 混合感染模型，以研究这些模型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，并提出了一种迫切需要的、生理相关的 HIV/HBV 共感染动物模型。我们相信我们的新恒河猴模型乙型肝炎病毒感染将成为乙型肝炎研究的前沿，并且在需要努力的关键时刻变得可用。现在正在转向治疗艾滋病毒和乙肝病毒的策略。鉴于迫切需要易于驯服的动物模型对于 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。