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Open AccessArticle

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

1
Public Health England, Manor Farm Road, Porton Down, Salisbury SP4 OJG, UK
2
Health Protection Research Unit in Emerging and Zoonotic Infections, National Institute for Health Research, Liverpool L3 5RF, UK
3
Clinical Virology, Regional Public Health Laboratory, Public Health England, Bordeseley Green East, Birmingham B9 5SS, UK
4
Institute of Infection and Global Health, University of Liverpool, Liverpool L3 5RF, UK
5
Centre for Genomics Research, University of Liverpool, Liverpool L3 5RF, UK
6
Singapore Immunology Network, A*Star, Biopolis, Singapore 138648, Singapore
*
Authors to whom correspondence should be addressed.
Viruses 2019, 11(11), 1023; https://doi.org/10.3390/v11111023
Received: 4 July 2019 / Revised: 25 October 2019 / Accepted: 29 October 2019 / Published: 4 November 2019
(This article belongs to the Collection Advances in Ebolavirus, Marburgvirus, and Cuevavirus Research)
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. View Full-Text
Keywords: Ebola virus; Makona; West Africa; transcriptomics; proteomics Ebola virus; Makona; West Africa; transcriptomics; proteomics
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Bosworth, A.; Dowall, S.D.; Armstrong, S.; Liu, X.; Dong, X.; Bruce, C.B.; F. P. Ng, L.; Carroll, M.W.; Hewson, R.; Hiscox, J.A. Investigating the Cellular Transcriptomic Response Induced by the Makona Variant of Ebola Virus in Differentiated THP-1 Cells. Viruses 2019, 11, 1023.

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