PIN4 - Ifn-Gamma Could Enhance the Effect of Human Macrophages Against Ebola Virus by Changing their Gene Expression Profiles

Abstract

To study the effect and possible mechanism of IFN-γ against Ebola Virus (EBOV) in human macrophages (Monocyte macrophages, MM; Alveolar macrophages, AM) by bioinformatics, and to provide potential biomarkers and reference for the prevention and treatment for EBOV infection. The gene expression profile of GSE64997 was downloaded from the Gene Expression Omnibus (GEO) database. This dataset included IFN-γ treated macrophages (MDM: n=4; AM: n=3) and controls (IFN-γ untreated MDM: n=4; AM: n=3), then both infected with EBOV. Differentially expressed genes (DEGs, P＜0.05, False Discovery Rate＜0.05, Fold change ＞2) between the two groups of samples were identified, followed by their Gene Ontology(GO) Enrichment analysis and protein-protein interaction (PPI) analysis. R software v3.4.2, GenClip 2.0, STRING 10.5, Cytoscape 3.4.0 were used to perform the above analyses. The results showed that IFN-γ-treated macrophages did not further reduce EBOV RNA levels, suggesting IFN-γ could block key life cycle events such as EBOV replication. The gene expression profiles of EBOV infected AM and MM were obviously changed after IFN-γ treatment. 58 common DEGs were identified in both AM and MM (vs. IFN-γ untreated ones) and the expression of 58 DEGs were all significantly increased compared with those in controls (P=0.001). The 58 DEGs were mainly enriched in biological functions (the immune function, virus defense response, et al.) and involved in KEGG pathways (ISG15 antiviral signaling pathway, Antiviral signaling by IFN-stimulated genes, et al.). CXCL10, STAT1, and ISG15 were the cores in the PPI network of the 58 common DEGs. In the process of IFN-γ treated macrophages against EBOV, the RNA levels of macrophage did not reduce obviously, which may be related to the anti-virus activation. This result suggested that IFN-γ could be effective in anti-EBOV infection. CXCL10, STAT1 and ISG15 may play key roles in anti-EBOV of macrophages after IFN-γ treatment.