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Cell-free microRNA identified as biomarker for early diagnosis of Ebola.

Ebola virus disease (EVD) is a severe infectious disease which caused an epidemic in West Africa in 2013-2015, and has resulted in at least 10,000 confirmed deaths. Early diagnosis of EVD is not only essential for implementation of effective interventions, it also critical for prevention of the spread of infection.

Lack of early biomarkers has shown to lead to diagnostic delays in current massive EVD outbreak and international spread of EVD.  However, it is particularly difficult to diagnose EVD at an early stage.  Now, a study from researchers led by Nanjing University has identified an Ebola virus-encoded microRNA-like fragment which serves as a biomarker for early diagnosis. The study is published in the journal Cell Research.

Earlier studies from the group and other teams have demonstrated that microRNAs (miRNAs) produced by eukaryotic cells and viruses are present in human blood in highly stable, cell-free forms and these so called circulating miRNAs can serve as non-invasive biomarkers for the early diagnosis of various diseases, including viral diseases. Current methods to diagnose suspected Ebola virus infection include reverse transcription polymerase chain reaction, antigen-capture enzyme-linked immunosorbent assay, and immunoglobulin M and immunoglobulin G ELISA.  Since there are insufficient feasible methods established to diagnose EVD at early stage, the current study investigated whether Ebola-specific small non-coding RNAs could be detected in human blood.

The current study extrapolated a sequence of miRNA-like fragment encoded by EVDV using the principle of miRNA production in eukaryotes. Results show in cellular environment, the existing and maturation of the miRNA-like fragment in the presence of a cloned pre-miR sequence were verified.

The lab further identified the Ebola virus-encoded miRNA-like fragment in serum of EVD patients by qRT-PCR, Northern blotting and TA-cloning/sequencing.  Data findings show that this miRNA-like fragment existed in acute phase and disappeared in the recovery phase of EVD survivors. The researchers note that this miRNA-like fragment was detectable in EVD patients before development of viremia with detectable Ebola genomic RNA, suggesting that it is an earlier biomarker which is expected to advance the diagnosable window for EVD.

The team surmise that the currently identified miRNA-like fragment may function as an early biomarker of EVD to advance the diagnosable window and reduce the difficulties in the isolation and treatment of patients who develop suspicious symptoms. They go on to add that early diagnosis and isolation can reduce the transmission to well under one additional person per infected case, thereby minimizing the possibility of virus transmission to others.  For the future, the researchers state because the miRNA-like fragment of EBOV is highly conserved, it may predict and prevent Ebola outbreaks in the future if Ebola arises again.

Source: Nanjing University


An illustration of the Ebola virus. The central core contains coiled single-stranded RNA (yellow) enclosed in a protein coat (purple). This is further enclosed in a matrix protein layer (red) and envelope (green). On the viral surface are glycoproteins (pink) that latch on to a host cell.  Credit: Russell Kigntley/Science Photo Library.
An illustration of the Ebola virus. The central core contains coiled single-stranded RNA (yellow) enclosed in a protein coat (purple). This is further enclosed in a matrix protein layer (red) and envelope (green). On the viral surface are glycoproteins (pink) that latch on to a host cell. Credit: Russell Kigntley/Science Photo Library.



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