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Pathogenesis of HIV and HBV Co-Infection in a Humanized Mouse Model

人源化小鼠模型中 HIV 和 HBV 共感染的发病机制

基本信息

批准号：
10349595
负责人：
Zandrea Ambrose
金额：
$ 23.63万
依托单位：
UNIVERSITY OF PITTSBURGH AT PITTSBURGH
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：
2021-02-15 至 2023-01-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10349595
关键词：
Acquired Immunodeficiency Syndrome Address Adenovirus Vector Animal Model Anti-Retroviral Agents Antiviral Therapy Area Biocompatible Materials CD4 Lymphocyte Count CD4 Positive T Lymphocytes Cell Count Cells Cessation of life Chronic Chronic Hepatitis Chronic Hepatitis B Cirrhosis Clinical Development Disease Progression Engraftment Ethics Evaluation Genes Goals HIV HIV Infections Hematopoiesis Hepatitis Hepatitis B Infection Hepatitis B Therapy Hepatitis B Virus Hepatocyte Human Immune Immune system Immunocompromised Host Individual Infection Inflammation Interferon-alpha Life Liver Liver Fibrosis Liver diseases Longevity Macaca Methods Modeling Morbidity - disease rate Mus Na(+)-taurocholate-cotransporting peptide Outcome Pan Genus Pathogenesis Pathology Persons Pharmaceutical Preparations Pre-Clinical Model Prevention Primary carcinoma of the liver cells Research Risk Role Time Tissues Vaccines Variant Viral Pathogenesis Virus Virus Diseases Virus Replication adaptive immunity adeno-associated viral vector analog animal model development cancer therapy chronic infection chronic liver disease co-infection experience high risk human disease human fetus tissue humanized mouse immune function immune reconstitution immunodeficient mouse model improved liver function mortality mouse model novel novel strategies prevent receptor reconstitution response transmission process treatment research vaccine access viral DNA

项目摘要

Abstract Approximately 260 million people have chronic hepatitis B virus (HBV) infection, which leads to a spectrum of liver pathologies, including chronic hepatitis, cirrhosis, and hepatocellular carcinoma (HCC). HBV infection continues to be transmitted and is responsible for 40% of all HCC deaths worldwide. Almost 38 million people are infected with human immunodeficiency virus (HIV) globally, with approximately 10% of them chronically co- infected with HBV. Morbidity and mortality in HIV/HBV co-infection is higher than mono-infections and co- infection accelerates HBV-related liver disease with more frequent development of HCC, particularly when CD4 counts are low. Virologically suppressed co-infected individuals still experience increased liver fibrosis over time possibly due to ongoing chronic inflammation that occurs even during suppressed HIV infection. There are no cures for either HBV or HIV. Multiple unanswered questions remain regarding HIV/HBV co-infections, including the natural HBV disease course and assessment of liver disease, HBV reactivation after occult infection (HBV DNA in the absence of active replication), and improvements in antiviral treatments for both viruses. Hindering HIV/HBV co-infection pathogenesis and treatment research is the lack of a reliable animal model to study co-infection. Pre-clinical models are essential to evaluate mechanisms of infection as well as novel prevention methods, improved therapies, and curative strategies. We propose to characterize novel chimeric mice engrafted with a humanized liver and immune system from nonfetal human cells and tissues. In addition, we will evaluate HBV replication and liver disease progression during mono-infection and with either CD4 cell depletion or antiviral therapy. In addition, we will evaluate HIV/HBV co-infection with or without suppressive antiviral therapy. The goal is to improve the humanize mouse model to recapitulate human HBV mono-infection and HIV/HBV co-infection for the development of better therapies and curative strategies.

摘要