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CDC-Led Team Uses Sequencing to ID New Ebola Virus Behind Last Year's Outbreak in Uganda

NEW YORK (GenomeWeb News) – A newly-identified species of Ebola virus caused the hemorrhagic fever outbreak in western Uganda last fall, according to a new paper published online today in PLoS Pathogens.
 
More than a dozen years after the last Ebola virus was identified in Ivory Coast, scientists from the US and Uganda nailed down the new Ebola species using a combination of antigen capture, IgM and IgG ELISA, and random-primed pyrosequencing methods. The virus — dubbed Bundibugyo ebolavirus for the district where it was first reported — is genetically distinct from previously reported Ebola species, differing from its closest relative by more than 30 percent.
 
“Due to the sequence divergence of this new virus relative to all previously recognized ebolaviruses, these findings have important implications for design of future diagnostic assays to monitor Ebola [hemorrhagic fever] disease in humans and animals, and ongoing efforts to develop effective antivirals and vaccines,” lead author Jonathan Towner, of the US Centers for Disease Control and Prevention’s Special Pathogens Branch, and his colleagues wrote.
 
Ebola viruses belong to a family of viruses causing hemorrhagic fevers in humans. Four species — Zaire, Sudan, Reston, and Côte d’Ivoire— have been detected previously. The Zaire and Sudan species, which cause fatal infections between about half and 90 percent of the time, have been implicated in several large outbreaks over the past 30 years.
 
Last year, individuals from the Bundibugyo and Kikyo townships in western Uganda began turning up with hemorrhagic fever. An Ebola outbreak was confirmed in late November, though health officials say the outbreak may have started as early as September. By the time it subsided in late December 2007, the virus infected nearly 150 individuals and caused 37 deaths.
 
In an effort to identify the virus responsible for the outbreak, Towner and his colleagues, a collaboration of researchers from the CDC, the Uganda Virus Research Institute, the Uganda Ministry of Health, and Columbia University, collected 29 blood samples from infected individuals and shipped them to the CDC in Atlanta.
 
There, the researchers tested the samples using everything from antigen capture assays and a broadly reactive filovirus L gene-specific RT-PCR assay to highly-sensitive real-time RT-PCR assays designed to detect Zaire and Sudan ebolaviruses and Marburg viruses.
 
The tests fingered Ebola virus as the culprit behind the outbreak. But the species was distinct from any identified in the past.
 
To get a better idea of just what they were dealing with, the researchers used Roche 454 sequencing to sequence more than 70 percent of the new virus’ genome. The team sequenced just one of the strains, Towner told GenomeWeb Daily News, because there is typically little Ebola virus evolution during human-to-human spread. They used this draft sequence to develop a real-time RT-PCR-based assay specifically targeting the new Ebola species.
 
Though the antigen capture assay, which Towner called “the workhorse assay,” was already helping those on the ground identify infected individuals, the new molecular assay was also deployed towards the end of the outbreak.
 
While the assays did not change the treatment that infected individuals received, Towner explained, they did help with identifying and isolating infected individuals to curb the virus’ spread.
 
Next, the team used primer walking sequencing on the reference virus RNA to complete the entire genome sequences of the new virus, Bundibugyo ebolavirus, as well as the Côte d’Ivoire ebolavirus. The researchers then used the new sequences to do a phylogenetic analysis of all of the Ebola and Marburg virus species identified so far.
 
Their results suggest that Bundibugyo ebolavirus is most closely related to Côte d’Ivoire ebolavirus. That was surprising, the authors noted, given the geographic distance between Uganda and the Ivory Coast.
 
Even so, Towner said, the species are quite distantly related: the team’s analysis suggests the species differ in about a third of their nucleotides.
 
And based on the Ugandan outbreak, the Bundibugyo ebolavirus appears to have a lower case fatality rate than species found in Zaire and Sudan (about 36 percent compared with 80 percent to 90 percent for Zaire and 50 percent to 55 percent for Sudan).
 
So far, there are no obvious genetic differences that explain this disparity, Towner said, noting that scientists still aren’t sure why the species from Zaire is usually deadlier than the one from Sudan. 
 
Even so, knowing the genetic differences between the strains should be helpful not only for developing Ebola detection assays but also for screening potential antivirals and other interventions, the authors noted. “Current human prototype ebolavirus vaccines include Zaire and Sudan ebolaviruses,” the authors wrote. “Cross-protection studies will need to be done to assess whether vaccine designs will need to incorporate the Bundibugyo ebolavirus.”
 
But while it’s possible that Ebola genetics will eventually yield clues about potential drug targets, Towner cautioned that type of application is still a long way off. “There’s more of the biology of the virus that we need to know before we can start picking up targets,” he said.
 
In addition, there may still be holes in the Ebola phylogenetic tree that will be filled as new viruses emerge. “I would predict that there probably are other species — or at least strains — that we haven’t detected yet,” Towner said.
 
For his part, Towner said he is interested in trying to find organisms that carry the most recently discovered Ebola virus. “One of the things we’d like to do is go back to the site of the outbreak and try to determine what the reservoir might be,” he said.

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