期刊论文详细信息
BMC Genomics
Proteomics informed by transcriptomics for characterising differential cellular susceptibility to Nelson Bay orthoreovirus infection
Research Article
Kris Ford1  Antony Bacic1  James W. Wynne2  Wojtek P. Michalski2  Mary Tachedjian2  Brian Shiell2  Lawrence Mok3  David A. Matthews4 
[1] ARC Centre of Excellence in Plant Cell Walls School of BioSciences, The University of Melbourne, Melbourne, VIC, Australia;CSIRO, Australian Animal Health Laboratory, East Geelong, VIC, Australia;CSIRO, Australian Animal Health Laboratory, East Geelong, VIC, Australia;ARC Centre of Excellence in Plant Cell Walls School of BioSciences, The University of Melbourne, Melbourne, VIC, Australia;Department of Cellular and Molecular Medicine, School of Medical Sciences, University of Bristol, Bristol, UK;
关键词: Proteomics;    Transcriptomics;    Proteomics informed by transcriptomics;    PIT;    Immune;    Host;    Response;    Nelson bay;    Orthoreovirus;    Interferon;   
DOI  :  10.1186/s12864-017-3994-x
 received in 2017-02-26, accepted in 2017-08-01,  发布年份 2017
来源: Springer
PDF
【 摘 要 】

BackgroundNelson Bay orthoreovirus (NBV) is a fusogenic bat borne virus with an unknown zoonotic potential. Previous studies have shown that NBV can infect and replicate in a wide variety of cell types derived from their natural host (bat), as well as from human, mouse and monkey. Within permissive cells, NBV induced significant cytopathic effects characterised by cell-cell fusion and syncytia formation. To understand the molecular events that underpin NBV infection we examined the host transcriptome and proteome response of two cell types, derived from bat (PaKiT03) and mouse (L929), to characterise differential cellular susceptibility to NBV.ResultsDespite significant differences in NBV replication and cytopathic effects in the L929 and PaKiT03 cells, the host response was remarkably similar in these cells. At both the transcriptome and proteome level, the host response was dominated by IFN production and signalling pathways. The majority of proteins up-regulated in L929 and PaKiT03 cells were also up-regulated at the mRNA (gene) level, and included many important IFN stimulated genes. Further functional experimentation demonstrated that stimulating IFN signalling prior to infection, significantly reduced NBV replication in PaKiT03 cells. Moreover, inhibiting IFN signalling (through specific siRNAs) increased NBV replication in L929 cells. In line with the significant cytopathic effects seen in PaKiT03 cells, we also observed a down-regulation of genes involved in cell-cell junctions, which may be related to the fusogenic effects of NBV.ConclusionsThis study provides new multi-dimensional insights into the host response of mammalian cells to NBV infection. We show that IFN activity is capable of reducing NBV replication, although it is unlikely that this is solely responsible for the reduced replication of NBV in L929 cells. The molecular events that underpin the fusogenic cytopathic effects described here will prove valuable for identifying potential therapeutic targets against fusogenic orthoreovirus.

【 授权许可】

CC BY   
© The Author(s). 2017

【 预 览 】
附件列表
Files Size Format View
RO202311100616313ZK.pdf 3086KB PDF download
【 参考文献 】
  • [1]
  • [2]
  • [3]
  • [4]
  • [5]
  • [6]
  • [7]
  • [8]
  • [9]
  • [10]
  • [11]
  • [12]
  • [13]
  • [14]
  • [15]
  • [16]
  • [17]
  • [18]
  • [19]
  • [20]
  • [21]
  • [22]
  • [23]
  • [24]
  • [25]
  • [26]
  • [27]
  • [28]
  • [29]
  • [30]
  • [31]
  • [32]
  • [33]
  • [34]
  • [35]
  • [36]
  • [37]
  • [38]
  • [39]
  • [40]
  • [41]
  • [42]
  • [43]
  • [44]
  • [45]
  • [46]
  • [47]
  • [48]
  • [49]
  • [50]
  • [51]
  • [52]
  • [53]
  • [54]
  • [55]
  • [56]
  • [57]
  • [58]
  • [59]
  • [60]
  • [61]
  • [62]
  • [63]
  • [64]
  • [65]
  • [66]
  • [67]
  文献评价指标  
  下载次数:4次 浏览次数:2次