Transcriptional changes in WB and PBMC collected from Makona infected Cynomolgus macaques

Zaire Ebolavirus (ZEBOV) continues to pose a significant threat to human health as highlighted by therecent epidemic that originated in West Africa and the ongoing outbreak in the Democratic Republicof the Congo. Although the ZEBOV variant responsible for this epidemic (Makona) shares significantgenetic similarity with previously identified variants (Kikwit and Mayinga), recent reports suggestslower disease progression in nonhuman primates. However, the pathogenesis caused by the newvariant is not fully understood. We present the first comprehensive approach in understanding ZEBOVMakonapathogenesis in cynomolgus macaques by measuring changes in immune cell frequencies,plasma levels of immune mediators, and differentially expressed genes (DEGs) within whole blood (WB)and peripheral blood mononuclear cells (PBMC). Our combined approach revealed a link between: 1)increased interferon-stimulated gene expression, IFNa levels, and activated plasmacytoid dendriticcells; 2) higher proinflammatory gene expression, cytokine and chemokine levels, and non-classicalmonocytes; 3) gene signature of leukocyte activation and increased granulocytes; and 4) decreasedexpression of lymphocyte related genes and lymphopenia. In addition, our data strongly indicatedelayed disease progression as well as limited overlap (~30%) in host transcriptome changes followingZEBOV-Makona infection compared to ZEBOV-Kikwit. These observations provide novel insight intothe molecular mechanisms of ZEBOV-Makona pathogenesis.