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 Mire, Joan B. Geisbert, Robert Cross, Krystle N. Agans, Daniel Jeske, Ilhem Messaoudi, Thomas Geisbert

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Article number9730
JournalScientific Reports
Volume7
Issue number1
DOIs
StatePublished - Dec 1 2017

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Ebolavirus
Democratic Republic of the Congo
Infection
Disease Progression
Genes
Gene Expression
Lymphopenia
Western Africa
Macaca
Plasma Cells
Transcriptome
Chemokines
Granulocytes
Dendritic Cells
Interferons
Primates
Disease Outbreaks
Monocytes
Blood Cells
Leukocytes

ASJC Scopus subject areas

  • General

Cite this

Infection with the Makona variant results in a delayed and distinct host immune response compared to previous Ebola virus variants. / Versteeg, Krista; Menicucci, Andrea R.; Woolsey, Courtney; Mire, Chad; Geisbert, Joan B.; Cross, Robert; Agans, Krystle N.; Jeske, Daniel; Messaoudi, Ilhem; Geisbert, Thomas.

In: Scientific Reports, Vol. 7, No. 1, 9730, 01.12.2017.

Research output: Contribution to journalArticle

Versteeg, Krista ; Menicucci, Andrea R. ; Woolsey, Courtney ; Mire, Chad ; Geisbert, Joan B. ; Cross, Robert ; Agans, Krystle N. ; Jeske, Daniel ; Messaoudi, Ilhem ; Geisbert, Thomas. / Infection with the Makona variant results in a delayed and distinct host immune response compared to previous Ebola virus variants. In: Scientific Reports. 2017 ; Vol. 7, No. 1.
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