将人类细胞移植到免疫缺陷小鼠的腹腔中，用于快速检测乙型肝炎病毒复制。

Transplantation of human cells in the peritoneal cavity of immunodeficient mice for rapid assays of hepatitis B virus replication.

机构信息

Marion Bessin Liver Research Center, Cancer Research Center, Diabetes Research Center, Albert Einstein College of Medicine of Yeshiva University, Bronx, NY, USA.

出版信息

Xenotransplantation. 2011 Nov-Dec;18(6):380-9. doi: 10.1111/j.1399-3089.2011.00675.x.

DOI:10.1111/j.1399-3089.2011.00675.x

PMID:22168144

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3693184/

Abstract

BACKGROUND

Studies of natural hepatitis B virus infection must be restricted to humans or primates due to viral species-specificity. Alternative hepadnavirus animal models, e.g., woodchuck hepatitis virus in captive woodchucks, are not convenient, while in transgenic mice hepatitis B virus or viral proteins are expressed permanently through integrated genomes. Availability of small animal models that are easily produced and permit rapid assays will be quite helpful.

AIMS

We examined whether transplantation of human cells in the peritoneal cavity of mice will generate an appropriate mass of cells with hepatitis B virus replication.

METHODS

HepG2 2.2.15 cells were transplanted intraperitoneally into NOD/SCID mice. Replication of hepatitis B virus and viral gene expression was determined by analysis of blood and transplanted tissues with viral DNA and hepatitis B core antigen expression. Interruption of viral replication was examined.

RESULTS

After intraperitoneal transplantation with microcarrier scaffolds, 2.2.15 cells engrafted and proliferated in the peritoneal cavity of NOD/SCID mice. Hepatitis B virus replicated in transplanted 2.2.15 cells as shown by hepatitis B core antigen expression. Moreover, viral particles were secreted into the blood. Hepatitis B virus replication was susceptible to conventional antiviral drug therapy, such as lamivudine, as well as experimental antiviral gene therapy with a synthetic mimic of an antiviral cellular microRNA.

CONCLUSIONS

Intraperitoneal transplantation of human cells rapidly provided reservoirs of hepatitis B virus in mice. This simple xenotransplantation approach will be effective and convenient for studies of hepatitis B and other human viruses in vivo.

摘要

背景

由于病毒种属特异性，天然乙型肝炎病毒感染的研究必须仅限于人类或灵长类动物。替代嗜肝 DNA 病毒动物模型，例如在圈养的毛榉木鸭中发现的 woodchuck hepatitis virus（WHV），并不方便，而在转基因小鼠中，乙型肝炎病毒或病毒蛋白通过整合基因组永久表达。具有易于产生且允许快速检测的小型动物模型将非常有帮助。

目的

我们研究了将人类细胞移植到小鼠腹腔内是否会产生具有乙型肝炎病毒复制能力的适当数量的细胞。

方法

将 HepG2 2.2.15 细胞通过腹腔内移植到 NOD/SCID 小鼠中。通过分析血液和移植组织中的病毒 DNA 和乙型肝炎核心抗原表达来确定乙型肝炎病毒的复制和病毒基因表达。检测病毒复制的中断情况。

结果

在使用微载体支架进行腹腔内移植后，2.2.15 细胞在 NOD/SCID 小鼠的腹腔内植入并增殖。乙型肝炎核心抗原表达表明，2.2.15 细胞中乙型肝炎病毒复制。此外，病毒颗粒被分泌到血液中。乙型肝炎病毒的复制易受常规抗病毒药物治疗（如拉米夫定）以及使用抗病毒细胞 microRNA 模拟物的实验性抗病毒基因治疗的影响。