Circulating microRNA profiles of Ebola virus infection.
Early detection of Ebola virus (EBOV) infection is essential to halting transmission and adjudicating appropriate treatment. However, current methods rely on viral identification, and this approach can misdiagnose presymptomatic and asymptomatic individuals. In contrast, disease-driven alterations in the host transcriptome can be exploited for pathogen-specific diagnostic biomarkers. Here, we present for the first time EBOV-induced changes in circulating miRNA populations of nonhuman primates (NHPs) and humans. We retrospectively profiled longitudinally-collected plasma samples from rhesus macaques challenged via intramuscular and aerosol routes and found 36 miRNAs differentially present in both groups. Comparison of miRNA abundances to viral loads uncovered 15 highly correlated miRNAs common to EBOV-infected NHPs and humans. As proof of principle, we developed an eight-miRNA classifier that correctly categorized infection status in 64/74 (86%) human and NHP samples. The classifier identified acute infections in 27/29 (93.1%) samples and in 6/12 (50%) presymptomatic NHPs. These findings showed applicability of NHP-derived miRNAs to a human cohort, and with additional research the resulting classifiers could impact the current capability to diagnose presymptomatic and asymptomatic EBOV infections.
Diagnostic Systems Division, U.S. Army Medical Research Institute of Infectious Diseases, Fort Detrick, Frederick, MD, USA.
Janice
J
Duy
Diagnostic Systems Division, U.S. Army Medical Research Institute of Infectious Diseases, Fort Detrick, Frederick, MD, USA.
Jeffrey W
JW
Koehler
Virology Division, U.S. Army Medical Institute of Infectious Diseases, Fort Detrick, Frederick, MD, USA.
Anna N
AN
Honko
Diagnostic Systems Division, U.S. Army Medical Research Institute of Infectious Diseases, Fort Detrick, Frederick, MD, USA.
Randal J
RJ
Schoepp
Metabiota, Kenema, Sierra Leone.
Nadia
N
Wauquier
Metabiota, Washington, DC, USA.
Jean-Paul
JP
Gonzalez
Virology Division, U.S. Army Medical Institute of Infectious Diseases, Fort Detrick, Frederick, MD, USA.
M Louise
ML
Pitt
Virology Division, U.S. Army Medical Institute of Infectious Diseases, Fort Detrick, Frederick, MD, USA.
Eric M
EM
Mucker
Virology Division, U.S. Army Medical Institute of Infectious Diseases, Fort Detrick, Frederick, MD, USA.
Joshua C
JC
Johnson
Diagnostic Systems Division, U.S. Army Medical Research Institute of Infectious Diseases, Fort Detrick, Frederick, MD, USA.
Aileen
A
O'Hearn
Metabiota, Kenema, Sierra Leone.
James
J
Bangura
Metabiota, Kenema, Sierra Leone.
Moinya
M
Coomber
Diagnostic Systems Division, U.S. Army Medical Research Institute of Infectious Diseases, Fort Detrick, Frederick, MD, USA.
Timothy D
TD
Minogue
D000293:Adolescent; D000328:Adult; D000818:Animals; D015415:Biomarkers; D016000:Cluster Analysis; D019295:Computational Biology / Q000379:methods; D004195:Disease Models, Animal; D029043:Ebolavirus / Q000502:physiology*; D005260:Female; D020869:Gene Expression Profiling; D019142:Hemorrhagic Fever, Ebola / Q000097:blood / Q000175:diagnosis / Q000235:genetics* / Q000821:virology*; D054884:Host-Pathogen Interactions / Q000235:genetics*; D006801:Humans; D008253:Macaca mulatta; D008297:Male; D035683:MicroRNAs / Q000097:blood / Q000235:genetics*; D008875:Middle Aged; D019562:Viral Load; D055815:Young Adult
D015415:Biomarkers; D035683:MicroRNAs