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Infection with the Makona variant results in a delayed and distinct host immune response compared to previous Ebola virus variants.
- Source :
-
Scientific reports [Sci Rep] 2017 Aug 29; Vol. 7 (1), pp. 9730. Date of Electronic Publication: 2017 Aug 29. - Publication Year :
- 2017
-
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.
- Subjects :
- Animals
Biomarkers
Democratic Republic of the Congo
Ebolavirus classification
Gene Expression Profiling
Gene Regulatory Networks
Hemorrhagic Fever, Ebola epidemiology
Hemorrhagic Fever, Ebola genetics
Host-Pathogen Interactions genetics
Humans
Immunity, Innate
Immunomodulation
Leukocytes, Mononuclear immunology
Leukocytes, Mononuclear metabolism
Leukocytes, Mononuclear virology
Lymphocyte Activation immunology
Lymphopenia blood
Lymphopenia etiology
Macaca fascicularis
Oxidative Stress
T-Lymphocyte Subsets immunology
T-Lymphocyte Subsets metabolism
Transcriptome
Virus Replication
Ebolavirus immunology
Hemorrhagic Fever, Ebola immunology
Hemorrhagic Fever, Ebola virology
Host-Pathogen Interactions immunology
Subjects
Details
- Language :
- English
- ISSN :
- 2045-2322
- Volume :
- 7
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Scientific reports
- Publication Type :
- Academic Journal
- Accession number :
- 28852031
- Full Text :
- https://doi.org/10.1038/s41598-017-09963-y