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基于系统的方法研究甲型 H7N9 流感病毒感染人源和禽源细胞时宿主的反应。

A System Based-Approach to Examine Host Response during Infection with Influenza A Virus Subtype H7N9 in Human and Avian Cells.

机构信息

School of Biological Sciences, Nanyang Technological University, 60 Nanyang Drive, Singapore 637551, Singapore.

Bioinformatics Institute, 30 Biopolis Street, #07-01 Matrix Building, Singapore 138671, Singapore.

出版信息

Cells. 2020 Feb 15;9(2):448. doi: 10.3390/cells9020448.

DOI:10.3390/cells9020448
PMID:32075271
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7072757/
Abstract

Although the influenza A virus H7N9 subtype circulates within several avian species, it can also infect humans with a severe disease outcome. To better understand the biology of the H7N9 virus we examined the host response to infection in avian and human cells. In this study we used the A/Anhui/1/2013 strain, which was isolated during the first wave of the H7N9 epidemic. The H7N9 virus-infected both human (Airway Epithelial cells) and avian (Chick Embryo Fibroblast) cells, and each infected host transcriptome was examined with bioinformatic tools and compared with other representative avian and human influenza A virus subtypes. The H7N9 virus induced higher expression changes (differentially regulated genes) in both cell lines, with more prominent changes observed in avian cells. Ortholog mapping of differentially expression genes identified significant enriched common and cell-type pathways during H7N9 infections. This data confirmed our previous findings that different influenza A virus subtypes have virus-specific replication characteristics and anti-virus signaling in human and avian cells. In addition, we reported for the first time, the new HIPPO signaling pathway in avian cells, which we hypothesized to play a vital role to maintain the antiviral state of H7N9 virus-infected avian cells. This could explain the absence of disease symptoms in avian species that tested positive for the presence of H7N9 virus.

摘要

虽然甲型流感病毒 H7N9 亚型在几种禽类中循环传播，但它也能感染人类并导致严重疾病。为了更好地了解 H7N9 病毒的生物学特性，我们研究了该病毒在禽类和人类细胞中的感染宿主反应。在这项研究中，我们使用了在 H7N9 疫情第一波期间分离出的 A/Anhui/1/2013 株。H7N9 病毒感染了人类（气道上皮细胞）和禽类（鸡胚成纤维细胞）细胞，并用生物信息学工具检查了每个受感染宿主的转录组，并与其他代表性的禽源和人流感 A 病毒亚型进行了比较。H7N9 病毒在两种细胞系中诱导了更高的表达变化（差异调节基因），在禽类细胞中观察到更显著的变化。差异表达基因的直系同源映射确定了在 H7N9 感染过程中存在显著富集的共同和细胞类型途径。该数据证实了我们之前的发现，即不同的流感 A 病毒亚型在人类和禽类细胞中具有病毒特异性复制特征和抗病毒信号。此外，我们首次报道了禽类细胞中的新的 HIPPO 信号通路，我们假设该通路在维持 H7N9 病毒感染的禽类细胞的抗病毒状态方面发挥着重要作用。这可以解释为什么在检测到存在 H7N9 病毒的禽类物种中没有出现疾病症状。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ce68/7072757/26df3659ba70/cells-09-00448-g006a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ce68/7072757/be7ee82f9c86/cells-09-00448-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ce68/7072757/217121690ec5/cells-09-00448-g002a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ce68/7072757/4d93b064167c/cells-09-00448-g003a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ce68/7072757/fae87e035dfb/cells-09-00448-g004a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ce68/7072757/02a0a2370411/cells-09-00448-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ce68/7072757/26df3659ba70/cells-09-00448-g006a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ce68/7072757/be7ee82f9c86/cells-09-00448-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ce68/7072757/217121690ec5/cells-09-00448-g002a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ce68/7072757/4d93b064167c/cells-09-00448-g003a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ce68/7072757/fae87e035dfb/cells-09-00448-g004a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ce68/7072757/02a0a2370411/cells-09-00448-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ce68/7072757/26df3659ba70/cells-09-00448-g006a.jpg

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