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人诺如病毒NS1-2蛋白的转录组分析突显了其在小鼠单核细胞中的多功能作用。

Transcriptomic analysis of human norovirus NS1-2 protein highlights a multifunctional role in murine monocytes.

作者信息

Lateef Zabeen, Gimenez Gregory, Baker Estelle S, Ward Vernon K

机构信息

Department of Microbiology and Immunology, Otago School of Medical Sciences, University of Otago, 720 Cumberland St, Dunedin, 9054, New Zealand.

Otago Genomics and Bioinformatics Facility, University of Otago, Dunedin, 9054, New Zealand.

出版信息

BMC Genomics. 2017 Jan 5;18(1):39. doi: 10.1186/s12864-016-3417-4.

DOI:10.1186/s12864-016-3417-4
PMID:28056773
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5217272/
Abstract

BACKGROUND

The GII.4 Sydney 2012 strain of human norovirus (HuNoV) is a pandemic strain that is responsible for the majority of norovirus outbreaks in healthcare settings. The function of the non-structural (NS)1-2 protein from HuNoV is unknown.

RESULTS

In silico analysis of human norovirus NS1-2 protein showed that it shares features with the murine NS1-2 protein, including a disordered region, a transmembrane domain and H-box and NC sequence motifs. The proteins also contain caspase cleavage and phosphorylation sites, indicating that processing and phosphorylation may be a conserved feature of norovirus NS1-2 proteins. In this study, RNA transcripts of human and murine norovirus full-length and the disordered region of NS1-2 were transfected into monocytes, and next generation sequencing was used to analyse the transcriptomic profile of cells expressing virus proteins. The profiles were then compared to the transcriptomic profile of MNV-infected cells.

CONCLUSIONS

RNAseq analysis showed that NS1-2 proteins from human and murine noroviruses affect multiple immune systems (chemokine, cytokine, and Toll-like receptor signaling) and intracellular pathways (NFκB, MAPK, PI3K-Akt signaling) in murine monocytes. Comparison to the transcriptomic profile of MNV-infected cells indicated the pathways that NS1-2 may affect during norovirus infection.

摘要

背景

人诺如病毒（HuNoV）的GII.4悉尼2012株是一种大流行毒株，在医疗机构中引发了大多数诺如病毒疫情。HuNoV非结构（NS）1-2蛋白的功能尚不清楚。

结果

对人诺如病毒NS1-2蛋白的计算机分析表明，它与鼠类NS1-2蛋白具有共同特征，包括一个无序区域、一个跨膜结构域以及H-box和NC序列基序。这些蛋白还含有半胱天冬酶切割位点和磷酸化位点，表明加工和磷酸化可能是诺如病毒NS1-2蛋白的保守特征。在本研究中，将人源和鼠源诺如病毒全长以及NS1-2无序区域的RNA转录本转染至单核细胞中，并使用二代测序分析表达病毒蛋白的细胞的转录组图谱。然后将这些图谱与感染MNV的细胞的转录组图谱进行比较。

结论

RNA测序分析表明，人源和鼠源诺如病毒的NS1-2蛋白会影响鼠类单核细胞中的多种免疫系统（趋化因子、细胞因子和Toll样受体信号传导）和细胞内信号通路（NFκB、MAPK、PI3K-Akt信号传导）。与感染MNV的细胞的转录组图谱比较，表明了NS1-2在诺如病毒感染期间可能影响的信号通路。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/485c/5217272/3e2c6ba6ee72/12864_2016_3417_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/485c/5217272/eb138f2ab3f5/12864_2016_3417_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/485c/5217272/8d34191d30d2/12864_2016_3417_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/485c/5217272/87246917f342/12864_2016_3417_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/485c/5217272/35c76f9384fb/12864_2016_3417_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/485c/5217272/903b7bd349f3/12864_2016_3417_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/485c/5217272/5ccb2109d913/12864_2016_3417_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/485c/5217272/3e2c6ba6ee72/12864_2016_3417_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/485c/5217272/eb138f2ab3f5/12864_2016_3417_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/485c/5217272/8d34191d30d2/12864_2016_3417_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/485c/5217272/87246917f342/12864_2016_3417_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/485c/5217272/35c76f9384fb/12864_2016_3417_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/485c/5217272/903b7bd349f3/12864_2016_3417_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/485c/5217272/5ccb2109d913/12864_2016_3417_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/485c/5217272/3e2c6ba6ee72/12864_2016_3417_Fig7_HTML.jpg

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