Abstract
Ebola virus (EBOV) is a negative-strand RNA virus that replicates in the cytoplasm and causes an often-fatal hemorrhagic fever. EBOV, like other viruses, can reportedly encode its own microRNAs (miRNAs) to subvert host immune defenses. miRNAs are short noncoding RNAs that can regulate gene expression by hybridizing to multiple mRNAs, and viral miRNAs can enhance viral replication and infectivity by regulating host or viral genes. To date, only one EBOV miRNA has been examined in human infection. Here, we assayed mouse, rhesus macaque, cynomolgus macaque, and human samples infected with three EBOV variants for twelve computationally predicted viral miRNAs using RT-qPCR. Ten miRNAs aligned to EBOV variants and were detectable in the four species during disease with several viral miRNAs showing presymptomatic amplification in animal models. miRNA abundances in both the mouse and nonhuman primate models mirrored the human cohort, with miR-1-5p, miR-1-3p, and miR-T3-3p consistently at the highest levels. These striking similarities in the most abundant miRNAs during infection with different EBOV variants and hosts indicate that these miRNAs are potential valuable diagnostic markers and key effectors of EBOV pathogenesis.
Highlights
The most recent outbreak of Ebola virus disease (EVD) in West Africa in 2013–2016 caused over 28,000 reported cases and greater than 11,000 deaths[1], highlighting the need for accurate and rapid diagnostic tests for patient triage and management of disease spread[2]
Candidate Ebola virus (EBOV) pre-miRNA and mature miRNA sequences and their locations in the consensus genome are given in Supplementary Table S1
All miRNAs except miR-VP-3p derived from the complementary RNA strand, which is the coding strand
Summary
The most recent outbreak of Ebola virus disease (EVD) in West Africa in 2013–2016 caused over 28,000 reported cases and greater than 11,000 deaths[1], highlighting the need for accurate and rapid diagnostic tests for patient triage and management of disease spread[2]. Other groups demonstrated similar findings, with a second report using 102 EBOV/Makona genome sequences from the 2014 outbreak to predict four pre-miRNAs and seven mature miRNA candidates[12] This group computationally predicted 138 gene targets and their related signaling pathways for these miRNAs. This group computationally predicted 138 gene targets and their related signaling pathways for these miRNAs They showed that synthetic EBOV miRNAs can regulate the expression of several predicted target genes in HeLa cells. A third group used the EBOV/Boende-Lokolia variant[13] from the 2014 outbreak to predict one pre-miRNA encoding for two mature miRNAs14 They confirmed that these miRNAs were produced in mammalian cell lines by transfecting the pre-miRNA sequence into these cells, and further demonstrated in vitro that one of the miRNAs (miR-1-5p) suppresses the expression of importin-α5, a nuclear transport protein that interacts with EBOV and may influence viral virulence in vivo
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.