Infection with the Makona variant results in a delayed and distinct host immune response compared to previous Ebola virus variants.
Krista Versteeg, Andrea R Menicucci, Courtney Woolsey, Chad E Mire, Joan B Geisbert, Robert W Cross, Krystle N Agans, Daniel Jeske, Ilhem Messaoudi, Thomas W Geisbert
Author Information
Krista Versteeg: Galveston National Laboratory, Galveston, TX, USA.
Andrea R Menicucci: Division of Biomedical Sciences, University of California-Riverside, Riverside, CA, USA.
Courtney Woolsey: Galveston National Laboratory, Galveston, TX, USA.
Chad E Mire: Galveston National Laboratory, Galveston, TX, USA. ORCID
Joan B Geisbert: Galveston National Laboratory, Galveston, TX, USA.
Robert W Cross: Galveston National Laboratory, Galveston, TX, USA.
Krystle N Agans: Galveston National Laboratory, Galveston, TX, USA. ORCID
Daniel Jeske: Division of Biomedical Sciences, University of California-Riverside, Riverside, CA, USA.
Ilhem Messaoudi: Department of Molecular Biology and Biochemistry, University of California-Irvine, Irvine, CA, USA. imessaou@uci.edu.
Thomas W Geisbert: Galveston National Laboratory, Galveston, TX, USA. twgeisbe@utmb.edu.
Zaire Ebolavirus (ZEBOV) continues to pose a significant threat to human health as highlighted by the recent epidemic that originated in West Africa and the ongoing outbreak in the Democratic Republic of the Congo. Although the ZEBOV variant responsible for this epidemic (Makona) shares significant genetic similarity with previously identified variants (Kikwit and Mayinga), recent reports suggest slower disease progression in nonhuman primates. However, the pathogenesis caused by the new variant is not fully understood. We present the first comprehensive approach in understanding ZEBOV-Makona pathogenesis 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, IFNα levels, and activated plasmacytoid dendritic cells; 2) higher proinflammatory gene expression, cytokine and chemokine levels, and non-classical monocytes; 3) gene signature of leukocyte activation and increased granulocytes; and 4) decreased expression of lymphocyte related genes and lymphopenia. In addition, our data strongly indicate delayed disease progression as well as limited overlap (~30%) in host transcriptome changes following ZEBOV-Makona infection compared to ZEBOV-Kikwit. These observations provide novel insight into the molecular mechanisms of ZEBOV-Makona pathogenesis.
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