Transcriptomic signatures differentiate survival from fatal outcomes in humans infected with Ebola virus

Abstract

BackgroundIn 2014, Western Africa experienced an unanticipated explosion of Ebola virus infections. What distinguishes fatal from non-fatal outcomes remains largely unknown, yet is key to optimising personalised treatment strategies. We used transcriptome data for peripheral blood taken from infected and convalescent recovering patients to identify early stage host factors that are associated with acute illness and those that differentiate patient survival from fatality.ResultsThe data demonstrate that individuals who succumbed to the disease show stronger upregulation of interferon signalling and acute phase responses compared to survivors during the acute phase of infection. Particularly notable is the strong upregulation of albumin and fibrinogen genes, which suggest significant liver pathology. Cell subtype prediction using messenger RNA expression patterns indicated that NK-cell populations increase in patients who survive infection. By selecting genes whose expression properties discriminated between fatal cases and survivors, we identify a small panel of responding genes that act as strong predictors of patient outcome, independent of viral load.ConclusionsTranscriptomic analysis of the host response to pathogen infection using blood samples taken during an outbreak situation can provide multiple levels of information on both disease state and mechanisms of pathogenesis. Host biomarkers were identified that provide high predictive value under conditions where other predictors, such as viral load, are poor prognostic indicators. The data suggested that rapid analysis of the host response to infection in an outbreak situation can provide valuable information to guide an understanding of disease outcome and mechanisms of disease.Electronic supplementary materialThe online version of this article (doi:10.1186/s13059-016-1137-3) contains supplementary material, which is available to authorized users.

The role of mononuclear phagocytes in Ebola virus infection

“…In addition to up‐regulation and hypersecretion of pro‐ and anti‐inflammatory chemokines and cytokines that were previous appreciated to occur, changes in expression of a large number of previously unappreciated genes were identified. Expression of some of these correlated with survival . Of note, many cytokines/chemokines, identified in previous studies to have altered expression during EBOV infection, were not identified in these studies; however, differences in approach as well as differences between transcriptional and translational changes may partially account for this.…”

Different features of Vδ2 T and NK cells in fatal and non-fatal human Ebola infections

“…The ability of EBOV to impact the number of circulating lymphocytes has been extensively described in mice [4], in non human primates [3] and in humans [6]. A decrease in NK cells was shown in animal models [5] and recently suggested in humans by a molecular profiling approach [20]. Moreover, a specific early loss of both NK and γδ T-cells was described also in other acute hemorrhagic fever models [21,22].…”

Recombinant vesicular stomatitis virus vector vaccines for WHO blueprint priority pathogens

“…64 A transcriptomic analysis of blood RNA from EBOV-infected patients showed elevated expression levels of genes associated with interferons and acute phase signaling pathways. 65 Lower levels of inflammation correlated with virus clearance and robust EBOV-specific T-cell responses. Although these novel data provide insight into innate and adaptive immune responses, their contribution to protection in humans is still not defined.…”