Investigating the Cellular Transcriptomic Response Induced by the Makona Variant of Ebola Virus in Differentiated THP-1 Cells

Viruses

JulianA. Hiscox¹  Xuan Liu¹  Stuart Armstrong¹  Lisa F. P. Ng¹  Xiaofeng Dong²  Andrew Bosworth³  ChristineB. Bruce³  StuartD. Dowall³  MilesW. Carroll³  Roger Hewson³ 

[1] Health Protection Research Unit in Emerging and Zoonotic Infections, National Institute for Health Research, Liverpool L3 5RF, UK;Institute of Infection and Global Health, University of Liverpool, Liverpool L3 5RF, UK;Public Health England, Manor Farm Road, Porton Down, Salisbury SP4 OJG, UK;

关键词: ebola virus;    makona;    west africa;    transcriptomics;    proteomics;   

DOI  :  10.3390/v11111023

来源: DOAJ

【 摘 要 】

Recent studies have shown that transcriptomic analysis of blood samples taken from patients with acute Ebola virus disease (EVD) during the 2013−2016 West African outbreak was suggestive that a severe inflammatory response took place in acutely ill patients. The significant knowledge gained from studying the Makona variant, a cause of the largest known EVD outbreak, may be applicable to other species of ebolavirus, and other variants of the Ebola virus (EBOV) species. To investigate the ability of Makona to initiate an inflammatory response in human macrophages and characterise the host response in a similar manner to previously characterised EBOV variants, the human monocytic cell line THP-1 was differentiated into macrophage-like cells and infected with Makona. RNA-Seq and quantitative proteomics were used to identify and quantify host mRNA and protein abundance during infection. Data from infection with Reston virus (RESTV) were used as comparators to investigate changes that may be specific to, or enhanced in, Makona infection in relation to a less pathogenic species of ebolavirus.. This study found demonstrable induction of the inflammatory response, and increase in the activation state of THP-1 macrophages infected with Makona. NFκB and inflammation-associated transcripts displayed significant changes in abundance, reflective of what was observed in human patients during the 2013−2016 EBOV outbreak in West Africa, and demonstrated that transcriptomic changes found in Makona-infected cells were similar to that observed in Reston virus infection and that have been described in previous studies of other variants of EBOV.

【 授权许可】

Unknown