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斑马鱼幼鱼中稳定的人诺如病毒复制模型。

A robust human norovirus replication model in zebrafish larvae.

机构信息

KU Leuven-Department of Microbiology, Immunology and Transplantation, Rega Institute, Laboratory of Virology and Chemotherapy, Leuven, Belgium.

KU Leuven-Department of Pharmaceutical and Pharmacological Sciences, Laboratory for Molecular Biodiscovery, Leuven, Belgium.

出版信息

PLoS Pathog. 2019 Sep 19;15(9):e1008009. doi: 10.1371/journal.ppat.1008009. eCollection 2019 Sep.

DOI:10.1371/journal.ppat.1008009
PMID:31536612
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6752765/
Abstract

Human noroviruses (HuNoVs) are the most common cause of foodborne illness, with a societal cost of $60 billion and 219,000 deaths/year. The lack of robust small animal models has significantly hindered the understanding of norovirus biology and the development of effective therapeutics. Here we report that HuNoV GI and GII replicate to high titers in zebrafish (Danio rerio) larvae; replication peaks at day 2 post infection and is detectable for at least 6 days. The virus (HuNoV GII.4) could be passaged from larva to larva two consecutive times. HuNoV is detected in cells of the hematopoietic lineage and the intestine, supporting the notion of a dual tropism. Antiviral treatment reduces HuNoV replication by >2 log10, showing that this model is suited for antiviral studies. Zebrafish larvae constitute a simple and robust replication model that will largely facilitate studies of HuNoV biology and the development of antiviral strategies.

摘要

人类诺如病毒(HuNoVs)是食源性疾病最常见的原因,每年造成 600 亿美元的社会成本和 21.9 万人死亡。缺乏强大的小型动物模型极大地阻碍了对诺如病毒生物学的理解和有效治疗方法的开发。在这里,我们报告 HuNoV GI 和 GII 在斑马鱼(Danio rerio)幼虫中复制到高滴度;复制在感染后第 2 天达到峰值,至少可检测到 6 天。该病毒(HuNoV GII.4)可以连续两次从幼虫传代到幼虫。HuNoV 可在造血谱系细胞和肠道细胞中检测到,支持双嗜性的概念。抗病毒治疗使 HuNoV 复制减少了 >2log10,表明该模型适合抗病毒研究。斑马鱼幼虫构成了一个简单而强大的复制模型,将极大地促进 HuNoV 生物学和抗病毒策略的开发研究。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7656/6752765/4c4a8d34bffd/ppat.1008009.g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7656/6752765/3573c8bee880/ppat.1008009.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7656/6752765/12e9dfe3680c/ppat.1008009.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7656/6752765/3c018feb0ab9/ppat.1008009.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7656/6752765/5f9e6760b648/ppat.1008009.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7656/6752765/61e1c120d0f8/ppat.1008009.g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7656/6752765/cc213dca58f5/ppat.1008009.g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7656/6752765/4c4a8d34bffd/ppat.1008009.g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7656/6752765/3573c8bee880/ppat.1008009.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7656/6752765/12e9dfe3680c/ppat.1008009.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7656/6752765/3c018feb0ab9/ppat.1008009.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7656/6752765/5f9e6760b648/ppat.1008009.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7656/6752765/61e1c120d0f8/ppat.1008009.g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7656/6752765/cc213dca58f5/ppat.1008009.g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7656/6752765/4c4a8d34bffd/ppat.1008009.g007.jpg

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