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I型干扰素受体敲除(A129)小鼠中寨卡病毒感染疾病进展的谱系依赖性差异。

Lineage-dependent differences in the disease progression of Zika virus infection in type-I interferon receptor knockout (A129) mice.

作者信息

Dowall Stuart D, Graham Victoria A, Rayner Emma, Hunter Laura, Atkinson Barry, Pearson Geoff, Dennis Mike, Hewson Roger

机构信息

National Infection Service, Public Health England, Porton Down, Salisbury, Wiltshire, United Kingdom.

出版信息

PLoS Negl Trop Dis. 2017 Jul 3;11(7):e0005704. doi: 10.1371/journal.pntd.0005704. eCollection 2017 Jul.

DOI:10.1371/journal.pntd.0005704
PMID:28672028
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5510909/
Abstract

Zika virus (ZIKV) falls into two lineages: African (ZIKVAF) and Asian (ZIKVAS). These lineages have not been tested comprehensively in parallel for disease progression using an animal model system. Here, using the established type-I interferon receptor knockout (A129) mouse model, it is first demonstrated that ZIKVAF causes lethal infection, with different kinetics of disease manifestations according to the challenge dose. Animals challenged with a low dose of 10 plaque-forming units (pfu) developed more neurological symptoms than those challenged with 5-log higher doses. By contrast, animals challenged with ZIKVAS displayed no clinical signs or mortality, even at doses of 106 pfu. However, viral RNA was detected in the tissues of animals infected with ZIKV strains from both lineages and similar histological changes were observed. The present study highlights strain specific virulence differences between the African and Asian lineages in a ZIKV mouse model.

摘要

寨卡病毒(ZIKV)分为两个谱系:非洲谱系(ZIKVAF)和亚洲谱系(ZIKVAS)。尚未使用动物模型系统对这些谱系在疾病进展方面进行全面的平行测试。在此,利用已建立的I型干扰素受体敲除(A129)小鼠模型,首次证明ZIKVAF会导致致命感染,根据攻击剂量不同,疾病表现的动力学也不同。用低剂量10个空斑形成单位(pfu)攻击的动物比用高5个对数剂量攻击的动物出现更多神经症状。相比之下,用ZIKVAS攻击的动物即使在106 pfu的剂量下也未表现出临床症状或死亡。然而,在感染了来自两个谱系的ZIKV毒株的动物组织中均检测到病毒RNA,并且观察到了相似的组织学变化。本研究突出了在ZIKV小鼠模型中非洲谱系和亚洲谱系之间毒株特异性的毒力差异。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1355/5510909/033d3e0f55da/pntd.0005704.g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1355/5510909/ecbffc81d7ce/pntd.0005704.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1355/5510909/45fc5de89af6/pntd.0005704.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1355/5510909/f1797583c20f/pntd.0005704.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1355/5510909/94a052447d8d/pntd.0005704.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1355/5510909/065f7ef79a82/pntd.0005704.g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1355/5510909/033d3e0f55da/pntd.0005704.g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1355/5510909/ecbffc81d7ce/pntd.0005704.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1355/5510909/45fc5de89af6/pntd.0005704.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1355/5510909/f1797583c20f/pntd.0005704.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1355/5510909/94a052447d8d/pntd.0005704.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1355/5510909/065f7ef79a82/pntd.0005704.g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1355/5510909/033d3e0f55da/pntd.0005704.g006.jpg

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