Gene Sleuths Identify Novel Hemorrhagic Fever Virus

In 2009, a fifteen-year-old boy walked into a rural health clinic in western Democratic Republic of the Congo (DRC) displaying symptoms of acute hemorrhagic fever, such as a severe nosebleed and bloody vomit and diarrhea. The young boy died in the clinic within 48-hours. Roughly one week later, a teenage girl came to the same health center, exhibiting similar symptoms indicative of hemorrhagic illness. She too died, within three days of symptom onset. Both patients were treated by a male nurse, who developed symptoms shortly after the girl’s death. Luckily, this third, and last, case was quickly transferred to the regional hospital, where he was treated and survived the sudden onslaught of disease.

Finally, three years after the illness was first documented, scientists are able to identify the viral culprit. The Bas-Congo Virus (BASV), named after the province in which it was first detected, is the newest addition to the group of deadly hemorrhagic fever viruses, such as Ebola and Marburg.  The discovery was published last week in the journal PLoS Pathogens.

Determining this causative agent warranted genuine detective work utilizing modern technology and techniques far more complicated than Sherlock Holmes could ever have imagined. The study’s scientists turned to “deep sequencing”, a multi-part method that generates millions of DNA sequences from a clinical sample. These sequences are then pieced together to create the viral genome. In this case, scientists were able to construct 98.2 percent of the BASV’s genetic code, using a blood sample from the lone survivor. This information is critical to distinguish it as a truly novel virus, as well as to determine closely related pathogens that may offer clues to further describe its pathogenicity and mode of transmission.

Deep sequencing revealed that BASV has some truly unique characteristics. Prior to this discovery, all known hemorrhagic viruses fell into one of four families—Filoviridae, Arenaviridae, Flaviviridae, or Bunyaviridae. Interestingly, BASV is more closely related to the rabies and Chandipura virus, which are part of the Rhabdovirus family. However, as the first of its kind to cause hemorrhagic disease, BASV is the sinister, distant cousin of this particular virus family. Genetic sleuthing further suggests that although evidence remains inconclusive, it is likely that BASV is a recently emerged zoonotic disease that was passed on to humans via insect bites. Considering the pattern of transmission from patient to healthcare worker, and existing evidence from other viral hemorrhagic fever outbreaks, human-to-human transmission of BASV is also possible. Further, since there are only three existing cases, waterborne or airborne transmission is unlikely. Nevertheless, it is difficult to establish the precise mode of transmission without knowing the natural reservoir.

The DRC has suffered from intermittent hemorrhagic disease outbreaks for decades, up to 20 percent of which have never been diagnosed. The discovery of BASV is therefore remarkable, but not necessarily surprising. As technology advances and gene sequencing develops further, it is likely that other novel viruses will be discovered before an outbreak occurs. Identifying the disease agent is the first critical step to control and eventually stop newly emerging diseases. 

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