title: A comparison of host gene expression signatures associated with infection in vitro by the Makona and Ecran (Mayinga) variants of Ebola virus.
abstract: The Ebola virus (EBOV) variant Makona (which emerged in 2013) was the causative agent of the largest outbreak of Ebola Virus Disease recorded. Differences in virus-host interactions between viral variants have potential consequences for transmission, disease severity and mortality. A detailed profile of the cellular changes induced by the Makona variant compared with other Ebola virus variants was lacking. In this study, A549 cells, a human cell line with a robust innate response, were infected with the Makona variant or with the Ecran variant originating from the 1976 outbreak in Central Africa. The abundance of viral and cellular mRNA transcripts was profiled using RNASeq and differential gene expression analysis performed. Differences in effects of each virus on the expression of interferon-stimulated genes were also investigated in A549 NPro cells where the type 1 interferon response had been attenuated. Cellular transcriptomic changes were compared with those induced by human respiratory syncytial virus (HRSV), a virus with a similar genome organisation and replication strategy to EBOV. Pathway and gene ontology analysis revealed differential expression of functionally important genes; including genes involved in the inflammatory response, cell proliferation, leukocyte extravasation and cholesterol biosynthesis. Whilst there was overlap with HRSV, there was unique commonality to the EBOV variants.
authors.affiliation: National Infection Service, Public Health England, Porton Down, Salisbury, UK.|National Institute of Health Research, Health Protection Research Unit in Emerging and Zoonotic Infections, Liverpool, UK.
authors.forename: Andrew
authors.initials: A
authors.lastname: Bosworth
authors.affiliation: National Infection Service, Public Health England, Porton Down, Salisbury, UK.|National Institute of Health Research, Health Protection Research Unit in Emerging and Zoonotic Infections, Liverpool, UK.
authors.forename: Stuart D
authors.initials: SD
authors.lastname: Dowall
authors.affiliation: Institute of Infection and Global Health, University of Liverpool, UK.
authors.forename: Isabel
authors.initials: I
authors.lastname: Garcia-Dorival
authors.affiliation: National Institute of Health Research, Health Protection Research Unit in Emerging and Zoonotic Infections, Liverpool, UK.|Institute of Infection and Global Health, University of Liverpool, UK.
authors.forename: Natasha Y
authors.initials: NY
authors.lastname: Rickett
authors.affiliation: High Containment Microbiology, Public Health England, Porton Down, Salisbury, UK.
authors.forename: Christine B
authors.initials: CB
authors.lastname: Bruce
authors.affiliation: School of Molecular and Cellular Medicine, University of Bristol, UK.
authors.forename: David A
authors.initials: DA
authors.lastname: Matthews
authors.affiliation: Centre for Genomics Research, University of Liverpool, UK.
authors.forename: Yongxiang
authors.initials: Y
authors.lastname: Fang
authors.affiliation: Institute of Infection and Global Health, University of Liverpool, UK.
authors.forename: Waleed
authors.initials: W
authors.lastname: Aljabr
authors.affiliation: Centre for Genomics Research, University of Liverpool, UK.
authors.forename: John
authors.initials: J
authors.lastname: Kenny
authors.affiliation: Centre for Genomics Research, University of Liverpool, UK.
authors.forename: Charlotte
authors.initials: C
authors.lastname: Nelson
authors.affiliation: Defence Science and Technology Laboratory, Porton Down, UK.
authors.forename: Thomas R
authors.initials: TR
authors.lastname: Laws
authors.affiliation: Defence Science and Technology Laboratory, Porton Down, UK.
authors.forename: E Diane
authors.initials: ED
authors.lastname: Williamson
authors.affiliation: Institute of Infection and Global Health, University of Liverpool, UK.
authors.forename: James P
authors.initials: JP
authors.lastname: Stewart
authors.affiliation: National Infection Service, Public Health England, Porton Down, Salisbury, UK.|National Institute of Health Research, Health Protection Research Unit in Emerging and Zoonotic Infections, Liverpool, UK.
authors.forename: Miles W
authors.initials: MW
authors.lastname: Carroll
authors.affiliation: National Infection Service, Public Health England, Porton Down, Salisbury, UK.|National Institute of Health Research, Health Protection Research Unit in Emerging and Zoonotic Infections, Liverpool, UK.
authors.forename: Roger
authors.initials: R
authors.lastname: Hewson
authors.affiliation: National Institute of Health Research, Health Protection Research Unit in Emerging and Zoonotic Infections, Liverpool, UK.|Institute of Infection and Global Health, University of Liverpool, UK.
authors.forename: Julian A
authors.initials: JA
authors.lastname: Hiscox
mesh_terms: D000072283:A549 Cells; D029043:Ebolavirus / Q000254:growth & development*; D020869:Gene Expression Profiling; D054884:Host-Pathogen Interactions; D006801:Humans; D018113:Respiratory Syncytial Virus, Human / Q000254:growth & development; D017423:Sequence Analysis, RNA; D059467:Transcriptome