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.

项目摘要 HIV和HBV都被认为是全球主要健康问题。艾滋病毒在全球感染了3700万人，而HBV感染了2.57亿。 HIV/HBV共感染是由于高度相似的传输途径而常见的估计有10％的HIV感染者也感染了HBV。除了他们类似的性和经皮的传播途径，HIV和HBV也具有驱动慢性感染的能力，肝脏功能障碍，肝纤维化和免疫衰竭。由于这些原因，与HIV和HBV共同感染是与较高的健康并发症概率有关，尤其是肝纤维化和肝细胞癌（HCC）。感染HIV感染的患者的可能性高达慢性HBV感染，并且具有更高的水平 HBV病毒血症。在HIV/HBV中看到的肝功能障碍和纤维化增加的机制目前尚不了解共同感染的个人。已经提出了多种假设，但是研究这些假设由于缺乏强大的HBV感染模型而阻碍了这些假设。因此，仍然需要开发新颖的，生理相关的HIV/HBV共同感染模型，以研究它们之间的相互作用病毒。在这里，我们介绍了HBV感染的第一个恒河猴模型，并提出了急需的，生理上相关的HIV/HBV共同感染动物模型。我们相信我们的新恒河猕猴模型 HBV感染将位于HBV研究的最前沿，并在关键时期开始使用现在正在转向艾滋病毒和HBV的治疗策略。鉴于迫切需要易于处理的动物模型在HIV/HBV共同感染中，我们认为本文提出的研究具有最高的意义。