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四种人源化NOD衍生小鼠模型用于登革病毒2型感染的评估

Evaluation of Four Humanized NOD-Derived Mouse Models for Dengue Virus-2 Infection.

作者信息

Gutierrez-Barbosa Hernando, Medina-Moreno Sandra, Perdomo-Celis Federico, Davis Harry, Chua Joel V, Zapata Juan C

机构信息

Institute of Human Virology, University of Maryland School of Medicine, Baltimore, MD 21201, USA.

Facultad de Biología, Universidad de Antioquia, Bogotá 050010, Colombia.

出版信息

Pathogens. 2024 Jul 30;13(8):639. doi: 10.3390/pathogens13080639.

DOI:10.3390/pathogens13080639
PMID:39204240
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11357684/
Abstract

Dengue is a significant public health problem with no specific viral treatment. One of the main challenges in studying dengue is the lack of adequate animal models recapitulating human immune responses. Most studies on humanized mice use NOD-scid IL2R gamma null (NSG) mice, which exhibit poor hematopoiesis for some cell populations. This study compares three humanized (hu) NOD-derived mouse models for dengue virus-2 (DENV-2) infection in the context of human cytokine expression. Three mouse strains (hu-NSG, hu-EXL, and hu-SGM3) received xenotransplants of human CD34+ fetal cord blood cells from a single donor, and one mouse strain received human peripheral blood mononuclear cells (hu-SGM3-PBMCs). All models exhibited infectious viruses in blood confirmed by plaque assay, but mice expressing human cytokines showed higher viremia compared to conventional NSG mice. The hu-SGM3-PBMCs model developed lethal infections, showing a significant increase in viremia and clinical signs. A detectable human cytokine response was observed in all the DENV-2-infected humanized mouse models. In conclusion, humanized NOD-derived mouse models expressing human cytokines offer a relevant platform for the study of dengue pathogenesis and antiviral therapies.

摘要

登革热是一个严重的公共卫生问题，目前尚无针对该病毒的特效治疗方法。研究登革热的主要挑战之一是缺乏能够模拟人类免疫反应的合适动物模型。大多数关于人源化小鼠的研究使用NOD-scid IL2Rγ基因敲除（NSG）小鼠，这类小鼠的某些细胞群体造血功能较差。本研究在人类细胞因子表达的背景下，比较了三种源自NOD的人源化（hu）小鼠模型对登革病毒2型（DENV-2）的感染情况。三种小鼠品系（hu-NSG、hu-EXL和hu-SGM3）接受了来自单一供体的人CD34+脐血细胞异种移植，一种小鼠品系接受了人外周血单个核细胞（hu-SGM3-PBMCs）。通过空斑试验证实，所有模型的血液中均存在感染性病毒，但与传统NSG小鼠相比，表达人类细胞因子的小鼠病毒血症水平更高。hu-SGM3-PBMCs模型出现了致死性感染，病毒血症和临床症状显著增加。在所有感染DENV-2的人源化小鼠模型中均观察到可检测到的人类细胞因子反应。总之，表达人类细胞因子的源自NOD的人源化小鼠模型为登革热发病机制和抗病毒治疗的研究提供了一个相关平台。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0291/11357684/883677ad873d/pathogens-13-00639-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0291/11357684/49afed3eda49/pathogens-13-00639-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0291/11357684/f47e38d75223/pathogens-13-00639-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0291/11357684/3ea23f7ee108/pathogens-13-00639-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0291/11357684/883677ad873d/pathogens-13-00639-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0291/11357684/49afed3eda49/pathogens-13-00639-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0291/11357684/f47e38d75223/pathogens-13-00639-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0291/11357684/3ea23f7ee108/pathogens-13-00639-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0291/11357684/883677ad873d/pathogens-13-00639-g004.jpg

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